The effects of phencyclidine (PCP) and its metabolites on serotonin (5-hydroxytryptamine, 5-HT) receptors were studied. PCP and its metabolites inhibited the uptake of [3H]5-HT and the binding of [3H]paroxetine in rat brain, while they failed to inhibit either [3H]5-HT binding to 5-HT1 receptors or [3H]ketanserin binding to 5-HT2 receptors. The trans-isomer of 4-phenyl-4-(I-piperidinyl)cyclo-hexanol (trans-4-PPC), the major metabolite of PCP, rather than PCP itself, inhibited [3H]5-HT uptake most potently. These results suggest that the serotonergic effects of PCP, in part, may be based on the effects of PCP metabolites on 5-HT uptake.