Illicit PCP is a major recreational drug and its growing clandestine production, distribution and use has become a major human public health concern. PCP and its new metabolites persisted for very prolonged periods in rat brain and adipose tissue after a single 25 mg/kg i.p. injection and showed accumulation after multiple dosing. The brain/plasma ratios for PCP between 0.5-48 h after injection ranged between 6-8.8 and adipose tissue/plasma ratios between 31-113. The concentrations of metabolites of PCP in rat brain (ng-eqt/g tissue) 1, 2 and 3 wk after a single 25 mg/kg i.p. injection of PCP were approximately 390, 230 and 74, respectively, and those of PCP 12, 6 and 5 ng/g, respectively. The long sojourn of PCP in adipose tissue and relatively slow egress therefore explains cumulative effects upon multiple dosing and raises the possibility of mobilization or release of large amounts of drug from fat stores in situations involving food deprivation, marked weight loss or stress. The persistence of PCP and its metabolites in brain and high degree of binding with melanin, implying a possible localization in neurmelanin-rich substantia nigra of midbrain and locus coeruleus of pons may help explain the prolonged duration of clinical effects and persistent neurological and cognitive dysfunction several days after PCP administration.