The effects of nifedipine on hemodynamics and pulmonary gas exchange were investigated in two patients with primary pulmonary hypertension. After 20 mg of the drug taken sublingually, pulmonary and systemic vascular resistances decreased, cardiac output increased, and blood oxygenation was improved. As assessed by the multiple inert gas elimination technique, nifedipine induced a deterioration in ventilation/perfusion (VA/Q) relationships consisting in an increased perfusion of units with low VA/Q. In spite of this negative effect on gas exchange, arterial PO2 increased as a consequence of increased mixed venous PO2 in relation to an augmented cardiac output, and in one patient there was a decrease in the secondary atrial shunt. Both patients were clinically improved by the nifedipine as a long-term treatment.