Human recombinant interleukin-4 (rIL-4) was assessed for its ability to promote the proliferative response of purified human B cells co-stimulated with submitogenic concentrations of soluble F(ab')2 fragments of anti-immunoglobulin (Ig) antibodies. The growth-promoting activity of rIL-4 was usually as potent as, or even more potent than, that of recombinant interleukin-2 (rIL-2), and more potent than that of recombinant interferon-gamma (rIFN-gamma). Preincubation with rIL-4 did not cause enhancement of the proliferative response of B cells to the subsequent addition of rIL-4 and anti-IgM antibody. In contrast, the proliferative response of B cells preincubated with anti-IgM antibody and rIL-4 was potentiated by the subsequent addition of rIL-4. The simultaneous addition of rIFN-gamma and rIL-2 or rIFN-gamma and rIL-4 had an additive effect in comparison with the response induced by rIL-2 or rIL-4 alone, respectively, whereas simultaneous addition of rIL-2 and rIL-4 induced a response equal or lower than that stimulated by rIL-2 or rIL-4 alone. The addition of rIFN-gamma at the beginning of culture or preincubation of B cells with rIFN-gamma and anti-IgM antibody potentiated the proliferative response of B cells to the subsequent addition of either rIL-2 or rIL-4. Taken together, these data suggest that rIL-4 acts as a growth factor for activated human B cells and displays on such cells a growth-promoting activity similar to that of rIL-2.