We gave captopril, an angiotensin converting-enzyme inhibitor, to four patients with unexplained pulmonary hypertension to see if it would lower pulmonary arterial pressure or pulmonary vascular resistance. The patients were studied at rest and during supine bicycle exercise, before and after 48 hours of captopril treatment (up to 450 mg/day). During the treatment, each patient was monitored, with systemic and pulmonary pressures measured hourly, and cardiac output every two to four hours. We found no significant effect of captopril, either at rest or with exercise, on the cardiac output, pulmonary artery pressure, or pulmonary vascular resistance, measured at the end of 48 hours treatment. We noted, however, that during the 48 hour period, all patients showed pronounced swings in their pulmonary and systemic artery pressures and cardiac outputs that had no relation to the administration of captopril or time of day. We conclude that captopril appears to be ineffective in causing a sustained reduction in the pulmonary artery pressure or pulmonary vascular resistance in patients with primary pulmonary hypertension. It appears, however, that these patients experience spontaneous variability in their pulmonary resistance from hour to hour which needs to be further studied before a reliable assessment of long-term drug treatment can be made.