AbstractIn rat pancreatic islet membranes exposed to [α–32P]NAD, cholera toxin stimulated the labelling of three peptides with Mr close to 22000, 42000 and 48000, respectively. In the islets, the toxin‐stimulated ADP‐ribosylation of the heavy form of the Ns α‐subunit predominated over that of the light from, in mirror image of the situation found in the exocrine pancreas. When intact islets were preincubated with cholera toxin, the adenylate cyclase activity of a subcellular particulate fraction was increased. The responsiveness of adenylate cyclase to GTP was also augmented, but that to NaF was decreased. In intact islets, the production of cyclic AMP and the glucose‐stimulated release of insulin were also enhanced after pretreatment with cholera toxin. These findings reveal the presence in pancreatic islets of the guanyl nucleotide regulatory protein of adenylate cyclase, with an unusual predominance of the heavy from of the N