Administration of small doses of radiolabeled phencyclidine hydrochloride (PCP X HCl) to normal volunteers has resulted in basic information on the disposition of PCP in humans. The drug and its metabolites were excreted mainly in the urine whether it was given orally or i.v. (73 +/- 4% of dose was recovered in urine after i.v. administration of 1 mg), with very little fecal excretion (3-5%) and some excretion in sweat. Oral bioavailability was 72 +/- 8%. Major metabolic pathways found involved hydroxylation of the cyclohexane and piperidine rings followed by conjugation. Oxidation to an aminopentanoic acid also occurred. PCP and phenylcyclohexene were inhaled when PCP was smoked. For PCP the weighted mean apparent terminal rate constant (beta) was 0.0395 +/- 0.0008 h-1 for 16 subjects, equivalent to a half-life of 17.6 h, but 2 subjects had half-lives of over 2 days. The volume of distribution (Vd, beta) was 6.2 +/- 0.3 liters/kg. At usual urinary pH, PCP excretion represented less than 10% of total clearance, but marked lowering of urinary pH can significantly increase the contribution of renal clearance to overall clearance.