Hypoxic pulmonary hypertension (HPH) is an important pathophysiological process. The mechanism of HPH is still not fully understood. Recent studies showed that hydrogen sulfide (H2S) could relax vascular smooth muscles and inhibit the proliferation of cultured vascular smooth muscle cells. Our study showed that both the gene expression of cystathionine gamma-lyase (CSE), one of the H2S generating enzymes, and the activity of CSE were suppressed in lung tissues during HPH. And the plasma level of H2S was decreased during HPH. Exogenous supply of H2S Could increase the plasma level of H2S, enhance CSE activity, and up-regulate CSE gene expression in lung tissue. At the same time, exogenous supply of H2S could oppose the elevation of pulmonary arterial pressure and lessen the pulmonary vascular structure remodeling during HPH. The results showed that endogenous H2S system was involved and exogenous H2S could exert beneficial effect on the pathogenesis of HPH. (C) 2003 Elsevier Science (USA). All rights reserved.