The role of nitric oxide in the regulation of adrenal steroidogenesis was examined in BALB/c mice by employing the nitric oxide synthase inhibitors NG-nitro L-arginine methyl ester (L-NAME) and NG-nitro L-arginine (L-NNA). The administration of a single dose of nitric oxide inhibitors (50 mg kg-1 body wt. i.p.) induced a fourfold increase in plasma corticosterone. Treatment with L-arginine (750 mg kg-1 body wt. s.c.), but not D-arginine, completely prevented corticosterone increases induced by L-NAME. To analyse whether the activation of adrenal steroidogenesis induced by nitric oxide synthase inhibitors involved the stimulation of the hypothalamo-pituitary-adrenal axis. ACTH levels were assessed. It was found that L-NAME significantly enhanced plasma ACTH concentrations. Genetic variations in this regulatory pathway are suggested by the fact that L-NAME increased corticosterone levels in BALB/c. C3H/He and DBA-2 mice, but not in C57BI/c mice, a strain characterized by a low steroid response to stress.