Transforming growth factor-beta 1 (TGF-beta 1) belongs to a family of polypeptides involved in the regulation of cell growth and differentiation. We have examined the ability of TGF-beta 1 to regulate isotype specific Ig secretion by murine spleen B cells. TGF-beta 1, in the presence of rIL-2, induced a synergistic 10-fold or greater increase in IgA secretion by LPS-stimulated spleen B cells. TGF-beta 1 alone had little to no effect on IgA secretion. In contrast, TGF-beta 1, with or without rIL-2, markedly inhibited IgG1 and IgM secretion under the same conditions. The costimulatory activity of TGF-beta 1 and rIL-2 on IgA secretion was seen in cultures of surface IgA negative B cells and was inhibited by anti-TGF-beta 1 antibody in a dose dependent manner. Vicia villosa agglutinin non-adherent Peyer's patch T cells, which secrete IL-2, also synergized with TGF-beta 1 and could substitute for the activity of LPS and rIL-2 on the IgA response. Finally, IL-5 added after 2 days of culture, but not at the beginning of culture, synergized with TGF-beta 1 on the IgA response. These studies indicate that TGF-beta 1 can interact with other lymphokines and selectively modulate the IgA response.