This study reports on the effects of TGF beta on the secretion of Ig isotypes by highly purified (> 99% CD20-positive) human peripheral blood B cells. Stimulation of these B cell preparations with EBV resulted in the secretion of IgM, IgG, and IgA and the addition of IL-4 induced readily detectable levels (> 100 ng/ml) of IgE between 10 and 25 days of culture. TGF beta 1 and TGF beta 2 showed similar dose-dependent suppression of IgM, IgG, and IgA, and the relative proportion of IgG and IgA remained unchanged in the presence of TGF beta. IgE production induced by EBV and IL-4 was significantly inhibited by TGF beta. TGF beta effects on Ig secretion were not related to inhibition of B cell proliferation by this cytokine. In contrast to these TGF beta effects on EBV activation of primary B cells, the constitutive Ig secretion by EBV-transformed B cells was resistant to TGF beta, while the increase in Ig secretion induced by IL-6 was inhibited by TGF beta. Thus, TGF beta inhibits the EBV-induced secretion of the major Ig isotypes in peripheral blood B cells and has differential effects on Ig secretion by transformed B cells.