The effects of prostaglandins PGD2, PGE1, PGE2, PGF2 alpha, and PGI2 on pulmonary vascular tone were investigated in normoxic and hypoxic unsedated newborn lambs with chronically implanted flow probes around right and left pulmonary arteries. Prostaglandins were injected into only one pulmonary artery, and direct effects of the compounds were determined by comparing the flow changes in the injected vs. the uninjected lung. PGD2 and PGF2 alpha were direct pulmonary vasoconstrictors, whereas PGE1, PGE2 and PGI2 were direct pulmonary dilators. Hypoxia augmented the vasodilation of PGE1 and PGI2 and diminished the constriction of PGD2 and PGF2 alpha; it also lowered the threshold for PGI2-induced dilation. While the E-type prostaglandins and PGI2 were both local dilators, they differed in that the systemic dilatory effects of the E-type agents exceeded their pulmonary effects, whereas the opposite occurred with PGI2. These results demonstrate that prostaglandins can act locally on pulmonary vascular smooth muscle tone in vivo and that the level of oxygenation or base-line vascular tone influences the pulmonary vascular responses to the PGs. Among the dilator prostaglandins, PGI2 appears to be more effective on the pulmonary rather than the systemic vascular bed under hypoxic conditions.