Polyclonal B cell activation is commonly observed in AIDS and in infection with HIV. The effect of HIV on the induction of B cell stimulatory factor 2 (BSF-2) production was examined, since BSF-2 plays an essential role in the differentiation of activated B cells to Ig-secreting cells. Increased BSF-2 mRNA levels and increased BSF-2 secretion were observed soon after exposure of mononuclear cells isolated from healthy donors to both "live" and inactivated HIV. HIV-induced BSF-2 production was seen in monocyte/macrophages, but not in T cells. These results suggest that the HIV-induced overproduction of BSF-2 might contribute to the polyclonal B cell activation seen in AIDS and in infection with HIV.