Vasodilator drugs were initially administered to patients with primary pulmonary hypertension based on the unproven hypothesis that pulmonary vasoconstriction played an important role in the pathogenesis of the disease. There were early reports of hemodynamic and clinical improvement after treatment with various vasodilating agents, but subsequent experience did not confirm these uncontrolled observations, and emphasized the limitations and hazards of this approach. Vasodilator therapy generally fails to reduce pulmonary vascular resistance selectively during long-term administration and frequently leads to systemic hypotension, exacerbation of the pulmonary hypertensive state, worsening of right ventricular failure, and systemic arterial desaturation. Beneficial hemodynamic responses are seen in only 15% to 25% of patients. Vasodilator therapy should not be considered an established treatment of patients with primary pulmonary hypertension.