113Cd-NMR experiments were performed to characterize the nature of Cd2+ binding to calmodulin in the presence of a tetradecapeptide mastoparan or a 26-residue peptide M13 (calmodulin-binding region of skeletal muscle myosin light-chain kinase). The results indicate that binding of these peptides to calmodulin induces a positive cooperativity between Ca2+ binding to C- and N-terminal domains. The results imply that the activation of myosin light-chain kinase caused by the increase in Ca2+ concentration occurs as a result of cooperative interactions not only between two Ca2+ binding sites in each domain but also between the two domains. The interdomain interaction manifests itself only in the presence of such peptides.