It has been reported that endogenous opioid antagonism through naloxone (NAL) blunts the hypotensive effect of captopril (CAP) in normal man. For this reason a study was carried out to determine whether NAL interacts with the antihypertensive effect of CAP in patients with mild-to-moderate essential hypertension (n = 6; age 22-43 years). Patients received, according to a randomized code, placebo (PL) during saline infusion, CAP (25 mg orally) during saline infusion, PL + NAL (0.4 mg as a bolus followed by a continuous infusion of 4.0 mg/h for 2 h) and CAP + NAL at the same doses. Three-day intervals elapsed between each phase of the study. Blood pressure (BP) and heart rate (HR) were recorded before (-20 to 0 min) and every 15 min for the next 2 h after drug administration. Blood samples for plasma renin activity (PRA), noradrenaline (NA) and aldosterone (ALD) were collected before (time 0) and 120 min after drug administration. Neither PL nor NAL changed any of the parameters examined, while CAP alone reduced mean BP to a highly significant extent. Naloxone did not change the hypotensive effect of CAP to any significant extent. Captropril, either alone or associated with NAL, tended to reduce plasma ALD and increase PRA (P less than 0.05) without changing HR or plasma NA. These data indicate that, at least under the experimental conditions used, endogenous opioid antagonism does not interfere with the haemodynamic and humoral effect of CAP in essential hypertensive man. This suggests that endogenous opioids do not mediate the pharmacological actions of CAP.