Plasma atrial natriuretic peptide (ANP) is an endogenous vasodilator, which might counteract pulmonary hypertension due to hypoxaemia. The aim of this study was to investigate the influence of acute and chronic hypoxia on plasma (ANP) concentrations in humans. Venous plasma ANP concentrations in six healthy subjects were measured before and after inhalation of hypoxic air (11% O2) at rest for 30 min, and following 5 min of mild hypoxic exercise (25 W). Pulmonary arterial plasma ANP levels were determined in 31 right heart catheterized patients with lung disease. In healthy subjects, mean arterial oxygen tension (Pao2) was 6.8 +/- 1.9 kPa after 30 min hypoxia at rest, and 4.7 +/- 0.9 kPa after hypoxic exercise testing. Hypoxia at rest did not induce significant changes in ANP concentrations, whereas hypoxic exercise led to significantly increased ANP levels. Among hypoxaemic patients, significantly elevated plasma ANP levels were found only in the subgroup with increased mean pulmonary artery pressure, but not in the subgroup with normal pulmonary artery pressure. In summary, severe acute hypoxia induced by hypoxic exercise, but not moderate acute hypoxia at rest, leads to increased ANP levels in healthy subjects. Chronic hypoxia alone does not lead to elevated plasma ANP levels; whereas, hypoxia combined with pulmonary hypertension causes increased plasma ANP concentrations in diseased subjects.