We have developed a model for the interaction of calmodulin and the presumptive calmodulin binding domain of rabbit skeletal muscle myosin light-chain kinase. In our model there is a bend in the central helix of calmodulin such that hydrophobic patches associated with the pairs of Ca2+ binding sites: I, II and III, IV; face one another. This was accomplished by altering the psi dihedral angle at one residue: Ser-81. We have made the presumptive calmodulin binding peptide alpha-helical over its entire length. In the model, this basic amphiphilic helix fits into a cavity formed by apposition of the two hydrophobic regions of calmodulin. We suggest that this general type of model may help explain calmodulin's ability to regulate the activities of its many different targets. Small changes in the conformation of a nonhelical bend within the central helix would have large effects on the relative positions of the two halves of the molecule. In this way, calmodulin might adapt itself to a wide range of possible calmodulin binding domains. The literature pertaining to the model is discussed. We also discuss the results of our own recent investigations of calmodulin species that have been altered by site-directed mutagenesis.