Effects of acute and chronic administration of phencyclidine (PCP) on heart rate (HR) and respiratory rate (RR) were studied in rhesus monkey. Acute administration of PCP (2.0 and 4.0 mg/kg i.v.) produced decrements in both HR and RR within 15 and 30 min after drug administration. Simultaneously, with this cardiorespiratory slowing, EEG tracings evidenced High-Voltage Slow-Waves (HVSW) and delta-waves. As HR and RR began to recover, High-Voltage Fast-Waves (HVFW) along with theta-waves developed in EEG recordings and persisted for 2–6 h, while both HR and RR were gradually returning to their respective pre-drug control levels. The intensity and duration of these PCP-induced effects were directly related to dosage level. Following chronic administration of PCP (daily dose of 2.0 or 4.0 mg/kg i.v.), its ability to produce cardiorespiratory alterations was significantly diminished along with a decrease in PCP-induced depression of EEG and behavioral activities. These results suggest that chronic PCP administration produces a tolerance to its depressant effect on HR, RR, EEG and behavioral activities in rhesus monkeys.