The effects of phencyclidine (PCP; 0.5, 1,5, 10 mg/kg, i.v.) on local cerebral glucose utilization (LCGU) in the rat were studied with the 2-deoxy-D-[1-14C]glucose method. Significant findings were obtained in 41 of 87 brain regions of PCP-treated rats (25-270% of control). Rates of LCGU increased throughout the limbic system, except the habenula. Although LCGU increased in most sensory structures, it decreased in specific layers of the somatosensory and auditory cortices and the inferior colliculus. Evidence was seen for dissociation between LCGU responses of specific thalamic relay areas and their terminal fields in the cortex. Increases in LCGU occurred throughout the motor system, manifesting a striking pattern of columnar activity in the motor cortex. However, LCGU was reduced in the frontal cortical pole. Elevated LCGU was observed in the pontine nuclei and the nuclei and the nucleus solitarius. Effects of 5 mg/kg PCP diminished with time although 8 regions maintained a metabolic alteration at 180 min. PCP induced several behaviors, including stereotypies, which varied with the dose and time after drug administration. The results demonstrate a PCP-induced activation of various functional circuits in the brain, especially the limbic system, and may provide a physiological basis for PCP's psychotomimetic properties.