The effect of interferon-gamma (IFN-gamma) antibody production by anti-mu- or pokeweed mitogen-stimulated bovine B cells was studied. IFN-gamma induced IgG2 secretion in isolated bulk B cell populations and in B cells sorted for IgM expression. IgM production was suppressed by the presence of IFN-gamma alone but this effect was antagonized by interleukin 2 (IL2). The effects of IFN-gamma on secreted levels of IgM, IgG1, and IgG2 correlated with the frequencies of cells expressing transcripts of the respective isotypes when stimulated with IFN-gamma-containing T cell supernatants. These results indicate that IFN-gamma plays a key role in IgG2 production in the bovine by directly affecting suitably stimulated B cells. The ability of IL2 to synergize with IFN-gamma to augment both the IgM and IgG2 responses implicates a TH1-like subset in regulation of this isotype.