Cardiovascular responses to the calcium antagonists verapamil and nifedipine were evaluated in a piglet model of hypoxic pulmonary hypertension. All animals were mechanically ventilated and paralyzed. Cardiac output (CO), pulmonary artery (Ppa) and aortic blood pressure (AoP), pulmonary wedge pressure, right atrial pressure (Pra), and arterial blood gases were measured prior to and after pulmonary hypertension was induced by hypoxia and after administration of calcium-blocking agents. Results were compared to a control group of piglets subjected to a similar period of hypoxia. Verapamil infusion (0.15 mg/kg) resulted in a rapid decrease in Ppa, AoP and pulmonary vascular resistance (p<0.05) which returned to baseline values by 15 min. Nifedipine (100 µg/ kg) resulted in a decrease in Ppa at 1 min (p<0.05) which remained significantly lower than controls throughout the study period. AoP declined precipitously during the same time period (p<0.01). No significant change in Ppa was noted when nifedipine was administered at a dose of 10 µg/kg. For the most part, these drugs have a transient vasodilatory action on pulmonary as well as systemic circulation in this animal model; however, they might in higher doses be associated with significant systemic hypotension. For this reason, the use of these drugs in the treatment of hypoxic pulmonary hypertension in the neonate should be approached with caution.