The benzomorphan opioid, SKF 10,047, is the prototypical agonist for the sigma receptor. In this study, pharmacological and autoradiographic analyses reveal that (+)-[3H]SKF 10,047 labels two sites in brain: a high affinity site resembling the sigma receptor and a second site, labeled with lower affinity by (+)-[3H] SKF 10,047, similar to the phencyclidine (PCP) receptor. The drug specificity of the high affinity site for (+)-[3H]SKF 10,047 resembles that of the putative sigma receptor labeled with (+)-[3H]-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine [(+)-[3H]-3-PPP], being potently inhibited by (+)-3-PPP, haloperidol and (+/-)-pentazocine, and demonstrating stereoselectivity for the (+)-isomer of SKF 10,047. In contrast, these drugs are weak in inhibiting binding of (+)-[3H]SKF 10,047 to the low affinity site, whereas PCP analogs, such as 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) and 1-[1-(m-aminophenyl)cyclohexyl]piperidine (m-NH2-PCP), are potent inhibitors. No stereoselectivity for the isomers of SKF 10,047 is noted at the low affinity binding site. Autoradiographic localizations of high affinity (+)-[3H]SKF 10,047 binding sites closely resemble those of (+)-[3H]-3-PPP labeled sites with high levels of binding in the hippocampal pyramidal cell layer, hypothalamus, pontine and cranial nerve nuclei and cerebellum. By contrast, low affinity (+)-[3H]SKF 10,047 sites are most abundant in nonpyramidal layers of the hippocampus, the cerebral cortex and thalamic nuclei, similar to the distribution of [3H]TCP labeled PCP receptors.