We studied the effects of recombinant interleukin 2 (rIL 2), interferon-alpha (rIFN-alpha) and interferon-gamma (rIFN-gamma) on proliferation and IgM synthesis of highly purified tonsillar B cells either without in vitro preactivation or after activation with Staphylococcus aureus Cowan 1 (SAC). Only rIL 2 affected tonsillar B cells not preactivated in vitro. It induced both proliferation and differentiation of B cells in a dose-dependent manner. rIL 2 induced proliferation of even Tac-negative B cells, but statistically significant responses were obtained only at high concentrations. The response was found also when no serum supplement was used in the culture medium. The finding suggests that tonsillar B cells express IL 2 receptors distinct from Tac antigen. When the cells were activated with SAC, significant proliferation was also found in response to rIFN-gamma. However, rIFN-gamma induced no IgM synthesis even after activation with SAC. rIFN-alpha affected neither B cell proliferation nor differentiation regardless of whether the cells were activated with SAC or not. Our results suggest that IL 2 can induce proliferation of activated B cells, but IFN-gamma only enhances proliferation of actively cycling B cells.