Susceptibility to inflammatory disease in infantile Lewis (LEW/N) female rats seems to be related to their impaired hypothalamo-pituitary-adrenal (HPA) axis response to different inflammatory stimuli, while the relative resistance to this type of disease in Fischer (F344/N) female rats is apparently due to their potent HPA axis response to the same stimuli. In the present study, we attempted to elucidate whether there is an impairment in the HPA axis response in the juvenile female LEW/N rat to inflammatory and noninflammatory stimuli, and also to determine whether the endogenous sex-steroid environment influences the HPA axis function in both strains of rats. For these purposes, juvenile F344/N and LEW/N rats of both sexes were submitted to different treatments: (a) inhalation of normal atmosphere or ether vapors for 1 min (Ether); (b) i.p. injection of vehicle alone or containing CRH (0.5 µg/rat), arginine vasopressin (AVP; 5 µg/rat), angiotensin II (AII; 5 µg/ rat), insulin (INS; 0.3 IU/rat), bacterial lipopolysaccharide (LPS; 100 µg/rat) or snake venom (SV; 100 µg/rat). Rats were then killed at different time intervals (in min) after treatments: 20 for Ether, AVP and CRH, 30 for AII, 45 for INS, 60 for SV and 120 for LPS. Our results indicate: (1) the existence of a clear sexual dimorphism in the rat HPA axis function under both basal and stress conditions, with a general hyperresponse in females compared with males to a variety of neuroendocrine stressors; in F344/N female rats, a hyperresponse to different inflammatory stimuli was also found; (2) a decreased ACTH secretion in plasma to CRH and inflammatory stimuli (LPS and SV) in LEW/N vs. F344/N female rats, and (3) an intact hypothalamo-corticotrope response to Ether, AII, INS and AVP treatments in female LEW/N rats. Our findings demonstrate the existence of a sexual dimorphic pattern in the rat HPA axis function, under basal and stimulated conditions, and further support the hypothesis that decreased corticotrope response to CRH-mediated events might be responsible for the high susceptibility of the LEW/N female rat to autoimmune dis