The localization of the guanylate cyclase (GC) activity has been established in the neocortex of adult guinea pigs by means of electron microscopical histochemistry [the DMSO-method of Fujimoto et al. (1981)]. Reaction product was deposited within a population of large- and medium-sized cortical neurons as well as in the cytoplasm of a part of the dendrites of variable size and in the cytoplasm and the nuclear membrane of a number of protoplasmic astrocytes. In the perikarya of the positive neurons, the reaction precipitate was mainly located within the cisterns of the rough endoplasmic reticulum and on the nuclear membrane. In the dendrites, the reaction product was usually distributed in close contact with microtubules, microfilaments, and beneath the postsynaptic membranes of a number of axodendritic synaptic contacts. The axons and all presynaptic boutons were negative. Thus, the localization of the GC could be determined as exclusively postsynaptic. The results obtained support the view for the probable participation of cyclic GMP in the cholinergic, glutaminergic or GABAergic, or peptidergic transmitter mechanisms in the central nervous system.