The regulator of G protein signaling (RGS) proteins modulate heterotrimeric G protein signaling. RGS8 was identified as a brain-specific RGS protein of 180 amino acids. Biochemical studies indicated that RGS8 binds to Galphao and Galphai3, and that it functions as a GTPase-activating protein (GAP) for Galpha subunits. Physiological investigations demonstrated that RGS8 is not a simple negative regulator, but accelerates the G-protein-coupled responses. In situ hybridization analysis showed a highly dense expression of RGS8 mRNA in Purkinje cells of the cerebellum in rat brain. When the cellular distribution of RGS8 was examined in non-neural cells transfected with RGS8 cDNA, the protein was found to be concentrated in nuclei. Further, co-expression of constitutively active Galphao resulted in the translocation of RGS8 protein to the plasma membrane. The cellular distribution of the RGS8 protein in cerebellar Pukinje cells was also studied in detail. It was shown that the protein is excluded from the nuclei and distributed in the cell body and dendrites except the axons of Purkinje cells. Thus, it is evident that there is a novel mechanism controlling the distribution of RGS8 protein in cerebellar Purkinje cells.