Receptor binding studies were carried out to test whether the rat brain phencyclidine (PCP) receptor is part of a K + channel. [ 3H]PCP, and two analogs, [ 3H]TCP and m-amino[ 3H]PCP, labeled a single receptor on rat brain synaptic membranes. Each compound bound to a similar number of sites ( B max = 2.7 pmol bound/mg protein); the apparent dissociation constants for these compounds ( K D < 0.3 μM) decreased with increasing temperature. The following observations indicate that the PCP receptor is part of a K + channel: (1) aminopyridines (AP) and tetraalkylammonium ions blocked [ 3H]PCP binding; their respective orders of potency, 4-AP = 3,4-diAP > 2-AP > 3-AP, and tetra-butylammonium (TBA) > tetraethylammonium > tetramethylammonium, paralleled their abilities to block K + channels, (2) the order of potency of PCP and its analogs for binding to the PCP receptor, TCP > PCE > m-amino-PCP > PCP > PCPY > m-nitro-PCP, paralleled their rank order for blocking brain K + channels, and (3) the stereospecific displacement of [ +H]PCP binding by the isomers of the “sigma” ligands, (+) N-allyl-normetazocine (NANM) > (−)NANM, and (−)cyclazocine > (+)cyclazocine, and of the dioxolanes, dexoxadrol > levoxadrol, paralleled their abilities to block brain K + channels. Reciprocal plot and Schild plot analyses indicated that TBA, (+)NANM and dexoxadrol were competitive inhibitors at the PCP receptor, whereas 4-AP had an allosteric interaction.