When calmodulin levels were determined in bovine lens layers at different ages, the values in the epithelial cell layer were strikingly higher than in the cortical layer and higher than in the nucleus. In the epithelial cell layer, except in very old animals, the calmodulin levels were maintained in adult animals. In the lens nucleus the extremely low level of calmodulin decreased during aging. In the cortical layer there were no systematic changes of calmodulin level during aging. In vitro, low calcium concentrations (micromolar) activated and higher calcium concentrations (over 100 microM) inhibited the lens adenylate cyclase activity. cAMP and cGMP degradation by phosphodiesterase was activated by calcium. It is suggested that calmodulin might be involved in the regulation of both adenylate cyclase and phosphodiesterase activities of lens epithelial cells and that free calcium plays a well-defined role in cAMP synthesis.