The neuronal cannabinoid receptor clone was expressed in Xenopus laevis oocytes as shown by the expression of saturable [ 3 H]WIN 55,212-2 binding sites. Co-expression of the cannabinoid receptor with cRNA coding for the G-protein-gated inwardly rectifying K + channel (GIRK1) resulted in oocytes exhibiting large inward K + currents in response to the cannabinoid agonist WIN 55,212-2. The activation of the potassium current by WIN 55,212-2 was dose-dependent with an EC 5 0 of 630 nM. These results suggest that activation of inwardly rectifying K + channels may be an additional effector mechanism for brain cannabinoid receptors.