Four hours after topical application of phencyclidine hydrochloride to hairless (hr-1/hr-1) mice, the mean hepatic concentration of phencyclidine (512.8 ng/g) was significantly lower for mice that had received intraperitoneal injections of sodium chloride, 1.75 mol/L (3500 mOsm/kg), than for control mice that had received equal volumes of water by the same route (2108.5 ng/g) (p less than 0.05). Hypertonic saline instilled intraperitoneally seemed to inhibit percutaneous absorption of phencyclidine hydrochloride. The effect may have been mediated by production of cutaneous dehydration.