Heterotrimeric GTP-dependent regulatory proteins (G-proteins) mediate modulation by many cell surface receptors. Activation of the G-proteins promotes dissociation of their alpha and beta gamma subunits. The similarity of behaviour of beta gamma subunits derived from a variety of G-proteins has led to their use as affinity reagents for the analysis of the more unique alpha subunits. The evolution of these uses is presented. One of the more insightful results was the isolation of a new class of G-protein alpha subunits (the alpha q subfamily) which have been shown to regulate the activity of a phospholipase C (PLC) specific for phosphatidylinositols. The experimental evidence leading to this conclusion is discussed. The activation by alpha q increases the apparent Vmax of the beta isoform of phosphatidylinositol-specific phospholipase C (PLC beta) and can be modulated by beta gamma subunits.