Sexual steroids are involved in the regulation of the immune system and modulate directly the synthesis of interleukin-1 (IL-1) by macrophages. Bacterial lipopolysaccharides (LPS) and IL-1 stimulate the hypothalamo-pituitary-adrenal (HPA) axis. As a result, glucocorticoids initiate a negative feedback loop since they inhibit the synthesis of IL-1. In this study we wanted to estimate the respective effects of genetic background, gender and sex-hormones (as assessed by gonadectomy) upon the HPA axis response to either IL-1 or LPS of mice of both sexes in 3 different strains: B6, CBA and B6 x CBA. Plasma ACTH and corticosterone, the predominant glucocorticoid in rodent, were determined by radioimmunoassay. IL-1 alpha or beta, 10 ng (per g. body weight), were injected i.p. and mice bled 2 h later. In the 3 strains, Il-1 alpha induced ACTH and IL-1 alpha and beta induced corticosterone responses, nearly 2-fold higher in females than in males. In the 3 strains, ovariectomy, as compared to sham operation, lowered the corticosterone values, while orchidectomy had no effect. LPS, 1.25 micrograms (per g. body weight), was injected i.p. and mice bled 2, 4 or 6 h later. The kinetics of the corticosterone response was sex- and strain-dependent. After 4 h, females of each strain had higher levels than males. Gonadectomy, as compared to sham operation, lowered the response of both males and females in the B6 strain, but was unefficient in the CBA one.(ABSTRACT TRUNCATED AT 250 WORDS)