Studies of the regulation of the IgE synthesis have been hampered by the difficulties in making lymphocytes produce IgE in vitro. Synthesis of IgE, IgG1 and IgM were investigated in a murine coculture system in which a conalbumin-specific T helper cell line of Th2 type was cultured together with nonadherent splenocytes from normal MHC-matched mice. Help provided by the antigen-stimulated T cell line induced significant IgE production (20 ng/ml), along with IgG1 (5 micrograms/ml) and IgM (250 micrograms/ml). Immunoglobulin synthesis in cultures was detectable at day 3-4 and culminated at day 7-8. IL-4 production was observed within the first 2 days of culture. The kinetics of the synthesis of the three isotypes were parallel. Stimulation of the Th2 cell line with Con A produced dose-response curves resembling those after antigen stimulation, whereas supernatant from these cells was unable to induce synthesis of IgE. The presence of interferon-gamma in the cultures, inhibited synthesis of IgE, IgM and IgG1, but this inhibition was not due to interference with the IL-4 production, which increased in the presence of high doses of interferon-gamma.