With critical illness, serum testosterone levels fall markedly while estrogen levels rise. Although animal studies suggest adaptive advantages, no prospective model has been available for studies in humans. We hypothesized that coronary artery bypass graft surgery (CABG) would provide such a model by eliciting the same reproductive hormone and other endocrine responses as reported with major nonsurgical illnesses. We further hypothesized that those responses would occur consistently in all CABG patients with predictable time courses providing reliable windows for prospective studies. In 17 men undergoing CABG, serum levels of reproductive hormones, cortisol, thyroid hormones, and IGF-1 were measured before and for up to 5 weeks after surgery. Changes in serum levels of reproductive and other hormones were similar to those reported in nonsurgical critically ill patients. Time course for onset, duration, and recovery of reproductive hormone changes were consistent among all patients. A window for studying the testosterone and estrogen responses was established as the first 5 days following CABG. Practical use of this model was demonstrated by evaluating, in another 7 men, changes in gonadotroph responsiveness to GnRH following CABG. Finally, to determine if our findings in CABG could be extended to other surgeries, we demonstrated similar endocrine responses in 12 men following abdominal aortic aneurysm resection (AAA). We conclude that patients undergoing CABG provide a useful human model for the prospective evaluation of the reproductive axis responses to acute illness.