The effect of exogenous transforming growth factor beta (TGF-beta) on Mycobacterium bovis BCG-induced tumor necrosis factor alpha (TNF-alpha) production by human mononuclear cells was studied. It was found that TNF-alpha production by human cells stimulated with BCG was significantly inhibited by TGF-beta. The specificity of the observed inhibition was demonstrated, since the addition of an anti-TGF-beta neutralizing monoclonal antibody completely reversed the inhibitory effect. Furthermore, the suppressive effect of TGF-beta on TNF-alpha secretion in this system was not due to a direct cytotoxic effect, since cell viability was comparable in the presence or absence of TGF-beta. Interestingly, our results demonstrated comparative suppressive effects of TGF-beta and interleukin-10 on BCG-induced TNF-alpha secretion. Together, the data demonstrate, for the first time, that TGF-beta inhibits BCG-induced TNF-alpha secretion by human cells.