Amphetamine and phencyclidine (PCP) are both proposed to exert effects on unconditioned behavior through dopaminergic mechanisms. However, a relatively complete characterization of their effects in rats reveals markedly different response profiles. Furthermore, whereas acute co-administration of amphetamine and PCP resulted in an increase in one component of stereotypy, repetitive head movements, two measures of locomotor activation, i.e., ambulation and nonfocused sniffing, were unchanged, and rearings were reduced. In addition, the response alterations which occur with repeated administration of these drugs did not display cross-sensitization. Thus, although repeated daily injections of amphetamine, which produced progressive locomotor augmentation, sensitized animals to the locomotor-stimulating effects of PCP, repeated PCP treatment, which also resulted in locomotor augmentation, decreased the locomotor response to a challenge injection of amphetamine. These findings suggest significant differences in the mechanisms underlying the effects of acute and repeated administration of PCP and amphetamine.