Plasma immunoreactive alpha-atrial natriuretic peptide (IR alpha-ANP) levels were determined before, and at 5 and 10 min after bolus intravenous administration of morphine (0.15 or 0.30 mg/kg) in 21 otherwise healthy human subjects who underwent elective surgery. Five min after injection IR alpha-ANP levels had nearly doubled in response to both doses of morphine. At 10 min, plasma IR alpha-ANP concentrations were lower than at 5 min in the 0.15 mg/kg group suggesting that IR alpha-ANP levels peak shortly after morphine administration. Morphine has been widely used in the treatment of acute left ventricular failure and ANP is a recently discovered hormone which possesses unique favourable effects in patients with congestive heart failure when administered exogenously. The combination of these data suggests an important potential role for ANP in the mechanism of action of morphine in the treatment of acute left ventricular failure.