Calmodulin interaction with Ca2+ may present a receptor mechanism analogous to the association of steroid hormones with cytoplasmic receptor proteins. In the systems examined to date, neither calmodulin nor Ca2+ alone have stimulatory effects. We have attempted to illustrate the similarities between the regulation of cellular events by Ca2+-calmodulin and the cyclic nucleotide system. If a general mechanism for calmodulin can be predicted it is to activate various enzymes to phosphorylate target proteins in a Ca2+-dependent manner. It is also of interest to point out the coorindate regulation of protein phosphorylation by Ca2+ and cAMP. Calmodulin can be considered to be involved in both types of reactions. This Ca2+-receptor not only activates Ca2+-dependent protein kinases directly but also plays an indirect role in cAMP-dependent phosphorylation by participating in the regulation of the intracellular steady-state levels of cAMP. The importance of calmodulin as a Ca2+-receptor and as a modulator of hormone action and endocrine cells illustrates the pleiotypic nature of this protein in both cellular and molecular aspects of endocrinology.