Reactivity and contractility of isolated pulmonary blood vessels of rats and dogs to two synthetic prostaglandin endoperoxide (PGH 2) analogs were studied. Canine pulmonary arteries were found to be insensitive to PGH 2 analogs ( i.e. U-46619 and U-44069 that were tested. In contrast, rat main pulmonary artery (EC50's = 4 x 10 −10 and 3.4 x 10 −9M, respectively) and canine intrapulmonary veins (EC50's = 3.3 x 10 −11 and 1. 1 x 10 −10M, respectively) responded to the endoperoxide analogs with potent and concentration-dependent contractile responses. This study demonstrates regional and species-related variability in the reactivity of pulmonary vascular smooth muscles to biologically, highly potent vasoactive agents. Endogenously generated and released PG-endoperoxides (PGH 2) may play important roles in the patho-physiology of the pulmonary vasculature.