Ten women with primary pulmonary hypertension had resting hemodynamic measurements taken before and after the nonparenteral administration of various vasodilators and prostaglandin inhibitors. Only sublingual isoproterenol, alone or combined with sublingual isosorbide dinitrate, effected a substantial (greater than 20%) drop in pulmonary vascular resistance; this decrease was accompanied by little change in pulmonary artery pressure. Isosorbide dinitrate was the only drug that elicited any reduction in pulmonary artery pressure; pulmonary vascular resistance decreased modestly. The oral administration of diazoxide, hydralazine, phentolamine, and tolazoline elicited little change in pulmonary artery pressure or resistance. Except for tolazoline, all these agents significantly decreased systemic blood pressure and resistance. Prostaglandin inhibition by indomethacin (acute and chronic dosing) increased pulmonary and systemic vascular resistances and reduced cardiac output. Aspirin combined with dipyridamole elicited no changes. The vasodilators and prostaglandin inhibitors studied evoked little improvement in resting pulmonary hemodynamic abnormalities in primary pulmonary hypertension.