Interleukin-6 (IL-6) mediates growth of murine B9 hybridoma/plasmacytoma cells via Ras-dependent mitogen-activated protein kinase (MAPK) pathway. Preincubation of cells with selective protein kinase C (PKC) inhibitors Gö6976 and Gö6983 leads to enhancement of IL-6-induced p44/p42 MAPK activity. The basal p44/p42 MAPK activity is also stimulated in the presence of both inhibitors. On the other hand, Gö6976 completely blocks proliferation, but Gö6983 which does not inhibit PKC(mu) has no effect on the cell growth. These findings suggest that PKC(mu) is required for proliferation and other PKC isoenzymes are involved in regulation of IL-6-dependent growth of B9 cells by negative regulation of the MAPK pathway.