The sigma receptor is a neuronal substrate that binds several psychoactive compounds. These include cocaine, some steroids, dextromethorphan, phencyclidine (PCP), and benzomorphans such as pentazocine and N-allyl-normatezocine (SKF-10047). Many newer atypical antipsychotic drugs also bind to the sigma receptor. The sigma receptor, however, is not the PCP receptor. The sigma receptor exists in the central nervous system, endocrine, immune and certain peripheral tissues. Progesterone and certain steroids have been shown to represent endogenous ligands for the sigma receptor. The sigma receptor resides likely in the nonsynaptic region of the plasma membrane. The sigma receptor exists in two forms: high-affinity and low-affinity. The solubilized sigma receptor retains all of the pharmacological characteristics of a membrane-bound receptor. A major physiological role of the sigma receptor may involve the modulation of a tonic potassium channel.