The purpose of the present study was to compare the acute and repeated administration of MK-801 (dizocilpine) on body temperature and behavior in the rat, and to determine whether there is cross-tolerance and/or cross-sensitization to phencyclidine (PCP) after repeated administration of MK-801. The acute administration of MK-801 increased body temperature, and this response was enhanced after repeated drug administration. PCP had little effect on body temperature in control rats, but produced increases in body temperature in rats treated daily with MK-801. The acute administration of MK-801 produced ataxia, locomotion, sniffing, and head-weaving, and after repeated drug administration both ataxia and head-weaving were reduced. PCP-induced ataxia, backpedalling, head-weaving, and turning behaviors were decreased in rats treated daily with MK-801, but PCP-induced locomotion and rearing were increased. These results indicate that there is cross-sensitization to the hyperthermic and locomotor effects of MK-801 and PCP, but there is cross-tolerance to some of the other behavioral effects of the drugs.