To elucidate the role of phospholipase Cbeta (PLCbeta) isozymes in the cerebellum, the distributions of PLCbeta3 and PLCbeta4 were examined in wild-type and PLCbeta4-deficient mutant mice using immunohistochemistry, and the functions were evaluated by measurement of type 1 metabotropic glutamate receptor (mGluR1)-mediated inward current and Ca(2+) mobilization. In wild-type mice, PLCbeta4 was distributed equally in both rostral and caudal cerebellum, while PLCbeta3 was enriched in the caudal versus the rostral cerebellum. In PLCbeta4-deficient mice, there was no measurable inward current or intracellular Ca(2+) elevation in the rostral cerebellum, whereas small responses were observed in the caudal cerebellum. In wild-type mice, the inward current was observed only following the release of caged GTPgammaS, not caged IP(3). These results suggest that the signal transduction machinery, including receptors, G-proteins, PLCbeta3, PLCbeta4, and effectors, form a functional unit, and the deletion of PLCbeta4 alters this unit, markedly changing signal transduction efficacy.