The effects of recombinant interleukin 2 (IL-2) on the in vitro differentiation of human tonsillar B cells which were not preincubated with Staphylococcus aureus Cowan I or with anti-human IgM were investigated. IL-2 was shown to induce the generation of Ig-containing cells in a dose-dependent fashion from 2.5 to 2,500 U IL-2/ml. Conversely, the quantities of Ig secreted in the culture supernatant were found in the majority of experiments to peak at 25 U/ml. The possible presence, in cultures stimulated with IL-2, of cells that were capable of synthesizing Ig but that did not secrete the Ig they have produced was investigated. Among a number of factors tested, we found that gamma-interferon, which did not trigger in vitro B cell differentiation when used alone, can induce an increased secretion of Ig without noticeable change in the number of Ig-containing cells in cultures stimulated with IL-2. The possibility that gamma-interferon and IL-2 act on subsequent steps of in vitro B cell differentiation is discussed.