Guanine nudeotide‐binding regulatory proteins similar to Gsand Gimay be involved in the activation of phospholipases C and A2by hormones and other ligands. The binding of hormones to receptors that activate phospholipase C is decreased by guanine nucleotides and these hormones also stimulate a high‐affinity GTPase activity in cell membranes. Effects of hormones on phospholipase C activity in cell‐free preparations are dependent on the presence of guanine nucleotides. In addition, fluoride and nonhydrolyzable GTP analogs activate phospholipases in a manner that can be blocked by GDPβS. The putative guanine nucleotide‐binding regulatory protein that appears to be involved in activation of phospholipase C is sensitive to pertussis toxin in some cells but not in others.— Fain, J. N.; Wallace, M. A.; Wojcikiewigz, R. J. H. Evidence for involvement of guanine nucleotide‐binding regulatory proteins in the activation of phospholipases by hormones.FASEB J, 2: 2569‐2574; 1988.