In a group of neonatal piglets an increase in pulmonary arterial pressure was obtained within 2 weeks after a partial mechanical obstruction of the left atrium by a balloon catheter. Mean pulmonary artery pressure in the hypertensive animals (n = 6) was 24 ± 2 mm Hg as compared (p < 0.01) with 15 ± 1 mm Hg in controls (n = 6) or 9 ± 2 mm Hg in sham-operated piglets (n = 6). Cardiac index was reduced in hypertensive versus control and sham groups: 0.15 ± 0.01 versus 0.32 ± 0.05 and 0.29 ± 0.04 L · min-1 · kg-1 (p < 0.05), respectively. There was no detectable difference on histologic examination in the pulmonary arteries between the three groups. Right ventricular hypertrophy was observed in the group with pulmonary hypertension. In hypertensive piglets, isolated conduit pulmonary arteries did not relax when stimulated with acetylcholine; they always relaxed to sodium nitroprusside. These data suggest that the first stages of perturbations reported during pulmonary venous hypertension occur at the level of the pulmonary vascular endothelium. This neonatal model of pulmonary hypertension is simple to perform and might be useful for further investigations.