Résumé : Pancreatic islets contain calmodulin. This protein activates adenylate cyclase in a subcellular fraction of rat islets in a calcium-dependent fashion. The Km for calmodulin was close to 0.1 microM, well below the concentration of endogenous calmodulin. Trifluoperazine and the trifluoromethylphenothiazine derivative of domperidone inhibited glucose-stimulated insulin release without affecting glucose oxidation by the islets. When insulin release was inhibited by 30% or more, this inhibition coincided with a reduction in the 45Ca net uptake by the islets. Both drugs suppressed the increment in adenylate cyclase activity evoked by calmodulin in a particulate fraction derived from the islets. However, the drugs also decreased basal and NaF-stimulated adenylate cyclase activities. Within limits, these data are compatible with the participation of endogenous calmodulin in the normal process of insulin release.