MANY hormones, neurotransmitters and growth factors, on binding to G protein-coupled receptors or receptors possessing tyrosine kinase activity, increase intracellular levels of the second messengers inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. This is due to activation of phosphoinositide-specific phospho-lipase(s) C (PLC), the isozymes of which are classified into groups, α, β, γ and δ (refs 1, 2). The β, γ and δ groups themselves contain PLC isozymes which have both common and unique structural domains³. Only the γl isozyme has been implicated in a signal transduction mechanism⁴. This involves association with, and tyrosine phosporylation by, the ligand-bound epidermal growth factor and platelet-derived growth factor receptors^5–7, probably by means of the PLC-γl-specific src homology (SH2) domain⁸. Because EGF receptor-mediated tyrosine phosphorylation of PLC-γ1 stimulates catalytic activity in vitro⁹ and G proteins have been implicated in the activation of PLC¹⁰, we investigated which PLC isozymes are subject to G protein regulation. We have purified¹¹ an activated G protein α subunit that stimulates partially purified phospholipase C and now report that this G protein specifically activates the β1 isozyme, but not the γ1 and δ1 isozymes of phospholipase C. We also show that this protein is related to the G_q class of G protein α subunits¹².