Reduced adenylyl cyclase activity after chronic ethanol exposure has been reported. In this study, we investigated by immunoblotting whether quantitative changes of adenylyl cyclase isoforms (type I, type II, and type V/VI adenylyl cyclases) exist in membrane preparations of the temporal cortex obtained from six alcoholics and six age-matched controls. The immunoreactivity of type I adenylyl cyclase decreased significantly in the temporal cortex of alcoholics when compared with controls (p < 0.05), whereas those of type II and type V/VI adenylyl cyclases showed no changes between the groups. These findings suggest that these isoform-specific afterations in the adenylyl cyclase system may be involved in the pathophysiology of alcoholism.