We studied the distribution of type II Ca2+/calmodulin (CaM)-insensitive adenylyl cyclase mRNA in the adult rat brain by in situ hybridization histochemistry. Although type II adenylyl cyclase mRNA was distributed throughout the rostrocaudal extent of the brain, the labeling intensity varied among regions. Strong expression was seen in fairly restricted regions such as CA1 and dentate-gyrus of the hippocampus, some thalamic nuclei, mammillary nucleus, dorsal raphe nucleus, parabrachial nucleus and locus coeruleus. The distribution of this type of mRNA was significantly different from that of type I Ca2+/CaM-sensitive adenylyl cyclase mRNA. The characteristic localization of type II mRNA suggests that this type of adenylyl cyclase may be involved in some neuronal functions different from the type I enzyme.