An investigation was made of endocrine changes occurring during the life history of Phascogale calura, a small, arboreal, squirrel-like insectivorous marsupial. Following a 3-week mating period in July each year, all males disappear from the population and it is presumed that they die. During the mating period the plasma cortisol concentration in males increased to a greater extent than did the plasma corticosterone. During this period the plasma concentration of CBG decreased in the males but not in the females, which resulted in competition between the two glucocorticoids for binding sites and a 25-fold sex difference in free cortisol concentration. The plasma testosterone concentration in males reached its maximum value about the time of disappearance of the males and the plasma lacked high-affinity binding for androgens. The depression in CBG concentration was androgen dependent since castration of captive males caused a marked increase in plasma CBG concentration which could be reversed with androgen administration. Postmorten examination of moribund males revealed evidence of hemorrhage from gastric ulcers and some evidence of immune suppression and disease. It is considered that a state of stress in males triggered by aggressive interactions following an elevation in plasma testosterone concentration during mating and antagonized by an androgen-dependent decrease in CBG concentration results in suppression of both immune and inflammatory reactions. This is the first detailed description of endocrine changes which accompany a stress-related total male mortality in a dasyurid marsupial species which does not belong to genus Antechinus.