Extensive mapping of the cannabinoid receptor in rat brain has been reported recently using synthetic cannabinoids. Another class of compounds, the aminoalkylindoles (AAIs), does not resemble the cannabinoids structurally. Ligand binding data on isolated membranes, however, indicate that AAIs bind to the cannabinoid receptor. The present experiments compared the binding of AAIs and synthetic cannabinoids in vitro and by receptor autoradiography. The AAIs bound to a receptor in rat cerebellum with high affinity (Kd = 15 nM), and synthetic cannabinoids were potent competitors for AAI binding sites. In the autoradiographic studies in rat brain, an AAI and a synthetic cannabinoid were used to compete for the binding of a radiolabeled AAI to compare regionally and quantitatively the inhibition of AAI binding by the two classes of compounds. The distribution of the AAI binding was very similar to that reported for synthetic cannabinoid binding. These data add further evidence that the aminoalkylindoles bind to the cannabinoid receptor. Furthermore, the autoradiographic data for AAI binding, in addition to the autoradiographic data for the synthetic cannabinoid, provide a high degree of confidence in the localization of the cannabinoid receptor in the rat brain.