Metaphit, 1-(1-(3-isothiocyanatophenyl) cyclohexyl) piperidine, an analog of phencyclidine (PCP) has been shown previously to selectively block PCP receptors and to irreversibly antagonize the depressant effect of PCP in cerebellum. In this study, we examined the electrophysiological interactions of metaphit and naloxone with stereoisomers of cyclazocine, an agent known to have analgesic and psychotomimetic activity in behavioral studies, effects that have been ascribed to opiate and PCP receptor activity. A dose-dependent and reversible slowing of Purkinje neuron discharge was seen with local application of (+)- or (-)-cyclazocine. We found that the blockade of (-)-cyclazocine effects required both high doses of naloxone and the presence of metaphit, whereas the responses to (+)-cyclazocine were blocked by metaphit alone on most cerebellar Purkinje neurons. These findings suggest that the depressant reaction of (+)-cyclazocine in cerebellar Purkinje neurons is primarily mediated through PCP receptors. (-)-Cyclazocine responses, on the other hand, appear to be due to activity at both PCP and kappa opioid receptors.