In Kitzmiller v. Dover Area School District, the first direct challenge brought in United States federal courts to an attempt to mandate the teaching of intelligent design on First Amendment grounds, Behe was called as a primary witness for the defense and asked to support the idea that intelligent design was legitimate science. Some of the most crucial exchanges in the trial occurred during Behe's cross-examination, where his testimony would prove devastating to the defense. Behe was forced to concede that "there are no peer reviewed articles by anyone advocating for intelligent design supported by pertinent experiments or calculations which provide detailed rigorous accounts of how intelligent design of any biological system occurred" and that his definition of 'theory' as applied to intelligent design was so loose that astrology would also qualify. Earlier during his direct testimony, Behe had argued that a computer simulation of evolution he performed with Snoke shows that evolution is not likely to produce certain complex biochemical systems. Under cross examination however, Behe was forced to agree that "the number of prokaryotes in 1 ton of soil are 7 orders of magnitude higher than the population it would take to produce the disulfide bond" and that "it's entirely possible that something that couldn't be produced in the lab in two years... could be produced over three and half billion years."
Many of Behe's critics have pointed to these exchanges as examples they believe further undermine Behe's statements about irreducible complexity and intelligent design. John E. Jones III, the judge in the case, would ultimately rule that intelligent design is not scientific in his 139-page decision, citing Behe's testimony extensively as the basis for his findings:
"Consider, to illustrate, that Professor Behe remarkably and unmistakably claims that the plausibility of the argument for ID depends upon the extent to which one believes in the existence of God."
"As no evidence in the record indicates that any other scientific proposition's validity rests on belief in God, nor is the Court aware of any such scientific propositions, Professor Behe's assertion constitutes substantial evidence that in his view, as is commensurate with other prominent ID leaders, ID is a religious and not a scientific proposition."
"First, defense expert Professor Fuller agreed that ID aspires to 'change the ground rules' of science and lead defense expert Professor Behe admitted that his broadened definition of science, which encompasses ID, would also embrace astrology. Moreover, defense expert Professor Minnich acknowledged that for ID to be considered science, the ground rules of science have to be broadened to allow consideration of supernatural forces."
"What is more, defense experts concede that ID is not a theory as that term is defined by the NAS and admit that ID is at best 'fringe science' which has achieved no acceptance in the scientific community."
"We therefore find that Professor Behe's claim for irreducible complexity has been refuted in peer-reviewed research papers and has been rejected by the scientific community at large."
"ID proponents primarily argue for design through negative arguments against evolution, as illustrated by Professor Behe's argument that 'irreducibly complex' systems cannot be produced through Darwinian, or any natural, mechanisms. However, … arguments against evolution are not arguments for design. Expert testimony revealed that just because scientists cannot explain today how biological systems evolved does not mean that they cannot, and will not, be able to explain them tomorrow. As Dr. Padian aptly noted, 'absence of evidence is not evidence of absence.'… Irreducible complexity is a negative argument against evolution, not proof of design, a point conceded by defense expert Professor Minnich."
"Professor Behe's concept of irreducible complexity depends on ignoring ways in which evolution is known to occur. Although Professor Behe is adamant in his definition of irreducible complexity when he says a precursor 'missing a part is by definition nonfunctional,' what he obviously means is that it will not function in the same way the system functions when all the parts are present. For example in the case of the bacterial flagellum, removal of a part may prevent it from acting as a rotary motor. However, Professor Behe excludes, by definition, the possibility that a precursor to the bacterial flagellum functioned not as a rotary motor, but in some other way, for example as a secretory system."
"Professor Behe has applied the concept of irreducible complexity to only a few select systems: (1) the bacterial flagellum; (2) the blood-clotting cascade; and (3) the immune system. Contrary to Professor Behe's assertions with respect to these few biochemical systems among the myriad existing in nature, however, Dr. Miller presented evidence, based upon peer-reviewed studies, that they are not in fact irreducibly complex."
"In fact, on cross-examination, Professor Behe was questioned concerning his 1996 claim that science would never find an evolutionary explanation for the immune system. He was presented with fifty-eight peer-reviewed publications, nine books, and several immunology textbook chapters about the evolution of the immune system; however, he simply insisted that this was still not sufficient evidence of evolution, and that it was not "good enough."
"With ID, proponents assert that they refuse to propose hypotheses on the designer's identity, do not propose a mechanism, and the designer, he/she/it/they, has never been seen. ... In addition, Professor Behe agreed that for the design of human artifacts, we know the designer and its attributes and we have a baseline for human design that does not exist for design of biological systems. Professor Behe's only response to these seemingly insurmountable points of disanalogy was that the inference still works in science fiction movies."
Jones would later say that Eric Rothschild's cross examination of Behe was "as good a cross-examination of an expert witness as I have ever seen. It was textbook."