In order to investigate the role of the adrenal gland in the pathogenesis of polycystic ovarian disease (PCOD), we evaluated the adrenal steroid response to an opiate receptor blockade. Six healthy menstruating volunteers and 6 patients with PCOD were given a saline or naloxone (4 mg i.v.) injection in the early follicular phase. Blood samples were taken prior to the injections and every 15-30 minutes in the following 2 hours. Cortisol, androstenedione (A) and dehydroepiandrosterone (DHA) plasma levels were determined by RIA after extraction (cortisol) and celite chromatography (A and DHA). While in controls naloxone increased only cortisol concentrations, in PCOD patients DHA plasma levels also were stimulated by the opiate receptor antagonist. In PCOD patients the increase of cortisol (p less than 0.05) and of DHA (p less than 0.001) levels resulted significantly higher than in controls. In both groups A plasma levels remained unchanged after naloxone administration. These data confirm that endogenous opioids exert an inhibitory control on the pituitary-adrenal axis. In PCOD patients the response to naloxone led to a hypersecretion of adrenal delta 5-androgens, which could account for the development of the syndrome.