Vasodilators have been a main focus of therapy for primary pulmonary hypertension. Adenosine and prostacyclin have been shown to reduce pulmonary vascular resistance acutely in these patients. In order to compare the acute hemodynamic effects of adenosine and prostacyclin, ten patients with severe primary pulmonary hypertension, unresponsive to medical therapy, were studied. After baseline hemodynamics were obtained, an adenosine infusion, 50 to 100 ng/kg/min, was begun and titrated to the maximum tolerated dose. Hemodynamics were allowed to return to baseline, and thereafter, a prostacyclin infusion was begun at 2 ng/kg/min, and titrated to the maximum tolerated dose. Overall, adenosine (200 +/- 53 ng/kg/min) produced a 33 +/- 18% (p < 0.001) fall in pulmonary vascular resistance and a 52 +/- 25% (p < 0.001) increase in cardiac output with no effect on pulmonary or systemic arterial pressures. Prostacyclin (8 +/- 4 ng/kg/min) caused a 22 +/- 18% (p < 0.01) fall in pulmonary vascular resistance and a 25 +/- 26% (p < 0.05) increase in cardiac output with a 14 +/- 6% (p < 0.001) decrease in systemic arterial pressure, but no change in pulmonary arterial pressure. The effects of adenosine and prostacyclin on pulmonary vascular resistance were similar (r = 0.70, r2 = 0.49, p = 0.02). Adenosine and prostacyclin have similar hemodynamic effects acutely in primary pulmonary hypertension. Adenosine may be useful as a test of the potential for long-term prostacyclin therapy in patients with primary pulmonary hypertension.