We studied the effects of ketamine and propofol on rat cultured mesangial cell (MC) proliferation. The 72-h exposure to ketamine (1-100 microM) inhibited [3H]thymidine incorporation into the MC in a concentration-dependent manner. Propofol, however, was not effective at inhibition of MC proliferation at doses from 1 to 100 microM. Ketamine also decreased the cell number at clinically relevant concentrations and increased adenosine 3',5'-cyclic monophosphate (cAMP) levels in MC. We also studied the effects of ketamine on cytokine-induced [3H]thymidine incorporation into the cells. Ketamine decreased the tumor necrosis factor-alpha (TNF-alpha)-, interleukin 1 (IL-1)-, and interleukin 6 (IL-6)-induced [3H]thymidine incorporation into the cells. It also decreased angiotensin II (Ag II)-induced [3H]thymidine incorporation. These results suggest that ketamine has inhibitory effects on MC proliferation, but that propofol does not. Because ketamine inhibits TNF-alpha-, IL-1-, and IL-6-induced MC proliferation, it may be useful in suppressing the cell growth clinically.