The efflux of cyclic guanosine 3',5'-monophosphate (cGMP) was studied from rat cerebellar slices which were stimulated by L-glutamate (1 mM), or by depolarizing concentrations of K+ (60 mM) or by the nitroso compound, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Via different mechanisms these agents stimulated cGMP synthesis producing several fold elevation of the cGMP content of the tissue slices. Simultaneously with the elevation of the intracellular (intra slice) concentrations of cGMP, a temperature-and time-dependent efflux of cGMP into the medium took place. This efflux was maximal at 5 min and could be inhibited by the known inhibitor of anion transport, probenecid, in a concentration-dependent manner. The results suggest the presence of an efflux system for cGMP, which may participate together with the well-characterized 3',5'-cyclic nucleotide phosphodiesterases in reduction of elevated cGMP levels.