It has not been clarified yet as to whether hypoxia and inflammation affect NO synthesis. In this study, we investigated the transcription of inducible nitric oxide synthase (iNOS) mRNA and the production of nitric oxide (NO) in rat smooth muscle cells (SMCs) cultured under hypoxic conditions in the presence and absence of proinflammatory cytokine interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS), We found that hypoxia inhibited the production of NO but did not affect the transcription of iNOS mRNA in rat SMCs treated with IFN-gamma, LPS, or both, These results indicate that O-2 is involved in the regulation of NO synthesis in inflammatory tissues. (C) 2000 Academic Press.