1. The present study investigated the effect of prior administration of nifedipine on AVP-induced ACTH release in seven normal volunteers. Three protocols were used: 20 mg oral nifedipine; 0.14 pressor units intramuscular (i.m.) per kg bodyweight aqueous AVP; oral nifedipine plus i.m. AVP 90 min later. Plasma ACTH and cortisol were measured at intervals for 2.5 h during each test. 2. The mean peak plasma ACTH and cortisol levels and the mean peak changes from basal in these levels were significantly lower in the nifedipine/AVP test than in the AVP alone test. The integrated area under the cortisol time curve was significantly lower for the nifedipine/AVP test than that for the AVP test alone. Nifedipine alone caused no changes in ACTH or cortisol. 3. Acute administration of oral nifedipine caused an inhibition of AVP-stimulated ACTH and cortisol release in normal humans. This effect may be due to blockade of plasma membrane calcium channels normally activated during AVP stimulation of pituitary corticotrophs.