The involvement of feline interleukin 6 (IL-6)-like activity in polyclonal B-cell activation in feline immunodeficiency virus (FIV) infection was investigated by using the proliferative response of hybridoma cell clone B3B1. Cats spontaneously infected with FIV had hyperimmunoglobulinemia, as shown by increases in the percentage of gamma-globulin and the plasma IgG concentration and decrease in the albumin/globulin (A/G) ratio. Because IL-6 plays an essential role in the differentiation of activated B cells into Ig-secreting cells, we examined the effect of FIV infection on the plasma IL-6 level. Plasma IL-6-like activity was found to be significantly higher in FIV-infected cats than in healthy controls. Peripheral blood mononuclear cells (PBMC) isolated from FIV-infected cats and cultured without any exogenous activators of IL-6 production released more feline IL-6-like activity than cells from healthy controls. This phenomenon was mainly due to the increase in the production of IL-6 by adherent cells such as monocytes/macrophages, but also partly by nonadherent cells. These results indicate that elevation of feline IL-6-like activity is associated with FIV infection and that overproduction of IL-6 may contribute to the polyclonal B-cell activation seen in FIV infection.