In Xenopus oocytes coinjected with poly(A)+ RNA derived from the rat cerebellum and cRNAs for the cloned G protein-gated inwardly rectifying K+ channel (GIRK), GIRK1 and GIRK2, the GABA-B agonist baclofen elicited inwardly rectifying K+ currents. The inward K+ currents elicited by baclofen were inhibited by the selective GABA-B antagonists 2-OH saclofen and CGP 35348, and by the GIRK inhibitor Ba2+. In contrast, baclofen caused no currents in oocytes injected with the cerebellar poly(A)+ RNA alone, the poly(A)+ RNA and cRNA for GIRK1 or GIRK2, or only cRNAs for GIRK1 and GIRK2. These findings indicate that GABA-B receptors in the rat cerebellum were functionally expressed in Xenopus oocytes and activated the cloned GIRKs composed of GIRK1 and GIRK2 as heteromultimers.