After 20 mg sublingual nifedipine in 12 men with clinical stable chronic cor pulmonale the mean arterial pressure and systemic vascular resistance fell, cardiac index rose, and mean pulmonary arterial (Ppa) and wedge (Ppaw) pressures, right atrial pressure, and PaO2 remained unchanged. After 20 mg orally every 6 hours for 24 hours in 11 patients, the mean arterial pressure fell further, systemic vascular resistance remained low, and the cardiac index returned to baseline, whereas the Ppa and Ppaw decreased, but the pulmonary vascular driving pressure (Ppa-Ppaw), right atrial pressure, PaO2, and spirometry and ejection fractions remained unchanged. Of eight patients receiving maintenance therapy four developed untoward side effects in 1 to 3 weeks and one was noncompliant. The remaining three patients evaluated at 6 weeks failed to improve and had unchanged resting hemodynamics. Thus in the absence of a potentially reversible hypoxic pulmonary hypertension, nifedipine may not improve pulmonary arterial pressure and cardiac function in clinically stable patients with cor pulmonale.