Whereas haloperidol more potently blocked the locomotion elicited by amphetamine (2.5 mg/kg i.p.) than that elicited by phencyclidine (PCP) (20.0 mg/kg s.c.), with inhibitory dose50s of 0.04 and 0.09 mg/kg s.c., respectively, clozapine more potently blocked the effect of PCP (0.04) than of amphetamine (8.8). Similarly, risperidone more potently blocked PCP (0.002) than amphetamine (0.2). In analogy to haloperidol, the selective dopamine D2 receptor antagonist, raclopride, antagonised amphetamine (0.16) more potently than PCP (0.8) whereas the selective 5-HT2A receptor antagonist, [R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4- piperidine-methanol] (MDL 100,907), only antagonised PCP (0.001) as compared to amphetamine (> 10.0). The potency for inhibition of PCP correlated more highly to affinity at 5-HT2A (r = 0.97, P < 0.01) than dopamine D2 (0.57, P > 0.05) sites, while the potency for blockade of amphetamine correlated more highly with affinity at dopamine D2 (0.94, P < 0.01) than at 5-HT2A sites (0.37, P > 0.05). In conclusion, in contrast to amphetamine, induction of locomotion by PCP is dependent upon functional 5-HT2A receptors, antagonism of which by 'atypical' antipsychotics underlies their ability to inhibit PCP-induced locomotion.