We have characterized the estrous cycle by obtaining vaginal smears, and quantitating estradiol (E), progesterone (P), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) plasma levels at different phases of the estrous cycle in Lewis (LEW/N) and Fischer (F344/N) rats. Comparison of the duration of the component phases of estrous showed LEW/N metestrous to be significantly longer than in F344/N rats while diestrous and estrous were significantly shorter; proestrous was identical. E levels in LEW/N rats were significantly greater than in F344/N rats only in the estrous phase of the cycle. P levels were significantly greater in LEW/N rats in all phases. LH and FSH levels in the two strains did not differ. Elevated E and P levels would be expected to be associated with increased corticosterone through inhibition of the glucocorticoid negative-feedback pathway. The data reported suggest that other modulating factors in corticotropin-releasing-factor synthesis/release could be overriding both the E and P effects upon hypothalamic-pituitary-adrenal axis responsiveness.