1. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have pulmonary vasorelaxant activity with plasma concentrations being elevated in patients with hypoxaemic pulmonary hypertension. However, their effects on acute hypoxic pulmonary vasoconstriction (HPV), the initiating stimulus for pulmonary hypertension have not to date been investigated. We have therefore studied the effects of ANP and BNP on acute HPV in humans. 2. Eight healthy volunteers were studied on three separate occasions. After reaching a resting haemodynamic state (t0), an infusion of either ANP (10 pmol kg-1 min-1), BNP (10 pmol kg-1 min-1) or placebo (5% dextrose) was commenced. This was given alone for 30 min (t30) before subjects were rendered hypoxaemic (SaO2 75-80%) for a further 30 min (t60), with the initial infusion continuing to t60. Pulsed-wave Doppler analysis of pulmonary artery flow was used to measure mean pulmonary arterial pressure (MPAP) and hence total pulmonary vascular resistance (PVR) was calculated. 3. MPAP and PVR both tended to decrease in response to ANP and BNP infusion, although compared with placebo, the difference at t30 was only statistically significant for PVR. Hypoxaemia increased MPAP and PVR, although values at t60 were significantly lower following both ANP and BNP compared with placebo. 4. In terms of the actual change in PVR (delta PVR) induced by hypoxaemia (from t30 to t60), BNP (146(16) dyn s cm-5), but not ANP (183(21) dyn s cm-5) significantly attenuated delta PVR compared with placebo (194(26) dyns s cm-5): mean difference BNP versus placebo 48 dyn s cm-5, 95% Cl 3-93. An identical pattern was observed for delta MPAP where BNP (15.9(1.1) mmHg), but not ANP (18.0(1.2) mmHg) significantly attenuated delta MPAP compared with placebo (19.0(1.7) mmHg): mean difference BNP versus placebo 3.1 mmHg, 95% Cl 0.7-5.5. 5. Thus, although both ANP and BNP exhibit pulmonary vasorelaxant activity, only BNP significantly attenuated the MPAP and PVR responses to acute hypoxaemia. This suggests that the natriuretic peptides may have a role in attenuating pulmonary hypertension secondary to hypoxaemia.