Guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC4.6.1.2.) was histochemically demonstrated in rat brain with light and electron microscopes by using a specific monoclonal antibody to soluble guanylate cyclase from rat brain. Under a light microscope, intense reactions were seen in caudate-putamen complex, neocortex and cerebellar cortex. Immunoreactive cells were mainly some types of neurons such as small neurons in caudate-putamen complex, Purkinje cells in cerebellar cortex and pyramidal cells in neocortex. Some astroglial cells were also stained. Not all neurons or glial cells exhibited the positive guanylate cyclase reactivity. Electron microscopic examination revealed that guanylate cyclase was localized within postsynaptic components (perikaryon and dendrites) in neurons and in the cytoplasm and plasma membrane of astroglia. Presynaptic terminals were free of reaction. The observation supports a possibility that cyclic GMP is involved in the postsynaptic events of neuronal transmission and the regulation of intracellular processes.