Inositide-specific phospholipase C (PLC) beta can be activated by the Gq family of G alpha subunits and by the G beta gamma subunits of heterotrimeric G proteins. PLC catalyzes the hydrolysis of phosphotidylinositol 4,5-bisphosphates (PIP2) to inositol trisphosphate (IP3) and diacylglycerol (DAG). This chapter describes a cell-based assay system to determine the activity of PLC by monitoring the levels of IPs in cultured cells. This assay system can be used to examine the activation of G protein-coupled receptors (GPCRs), coupling of GPCRs to G proteins, and the interactions of G proteins to PLC beta.