We examined the effect of interleukin-6 on the levels of cGMP and nitrite in rat hippocampal slices. Interleukin-6 at 400 ng/ml time dependently increased the content of cGMP of slices after incubation for 1, 2, 3, and 4 h, and the effect of interleukin-6 was maximal at 2 h post-incubation. In addition, exposure of slices to interleukin-6 at 80, 400 and 2000 ng/ml or at 16, 80 and 400 ng/ml for 2 h significantly elevated the cGMP level and nitrite level, respectively, in a concentration-dependent manner. Also, 0.1 mM N-G-nitro-L-arginine alone showed no effect on either the cGMP level or the nitrite level. However when incubated in conjunction with 400 ng/ml interleukin-6 for 2 h, N-G-nitro-L-arginine apparently prevented the increase in cGMP and nitrite induced by 400 ng/ml interleukin-6. The present results show that NO mediates the increase in cGMP induced by interleukin-6 and suggest that interleukin-6 may exert an inducible effect on the NO synthase in hippocampal slices.