Ventilation‐perfusion relationships of the lung (VA/Q) and central haemodynamics were studied in nine healthy subjects before and during 30 min of vasoactive intestinal polypeptide (VIP) infusion (20 ng kg‐min^‐1). During the infusion, arterial concentrations of VIP rose from 16‐1 6‐1 to 420 110 pmol 1^‐1 and noradrenaline concentrations doubled (P < 0–01). VA/Q distributions, determined by inert gas elimination technique, were significantly shifted to lower values for VA/Q with slight increases in dispersions, but arterial oxygen tension remained unchanged. Heart rate, stroke volume and cardiac output rose 27, 44 and 80% respectively (P < 0–01). Systematic arterial pressure stabilized at a slightly lower level compared to basal (base line: 93 5 mmHg, VIP: 88 6 mmHg, P < 0–05). Right atrial and pulmonary capillary wedge pressures remained unchanged during VIP infusion, while pulmonary vascular resistance and systematic vascular resistance decreased significantly, by 25% (P < 0–03) and 53% (P < 0–01), respectively. It is concluded that VIP causes: (1) alterations in ventilation‐perfusion distributions, but generates no shunt and does not cause hypoxaemia during 30 min infusion, (2) reduction of pulmonary and systemic vascular resistances and afterload reduction of the left ventricle, (3) reflex sympathoadrenal stimulation with increasing heart rate and myocardial contractility, and (4) a direct positive inotropic effect on the myocardium.