Platelet activating factor (PAF) treatment caused a transient rise in cyclic GMP levels in rat hippocampal slices. The stimulation of cyclic GMP synthesis induced by PAF was dose-dependent and was suppressed after treatment with PCA-4248, a PAF antagonist, a fact that could suggest the involvement of specific PAF receptors. In addition, when slices were incubated in the presence of N-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, PAF-stimulated cyclic GMP generation was abolished. Therefore, PAF activates guanylyl cyclase most probably via formation of NO. PAF also induced a time-dependent increase of NO synthase activity in hippocampal slices in correlation with the increase observed in cyclic GMP levels. (C) 1996 Academic Press, Inc.