Pleuritis is a common initial clinical manifestation of tuberculosis. It is associated with an accumulation of a variety of cytokines in the pleura and pleural fluid. We have recently shown that these proinflammatory cytokines induce the pleural mesothelial cell to produce large amounts of nitric oxide, a nitrogen intermediate that has been shown to have a tuberculocidal effect. TGF-beta has also been found in situ in tuberculous effusions and pleural tissues and is thought to suppress the immune response and promote tissue repair. This study examined the effects of TGF-beta on cytokine-induced NO synthesis by rat pleural mesothelial cells in vitro. Results demonstrated that TGF-beta significantly inhibited NO synthesis and that this inhibition was associated with a proportionate decrease in iNOS mRNA and iNOS protein. Suppression of pleural mesothelial cell NO synthesis by TGF-beta may be important in the pathogenesis of tuberculous pleuritis.