Cd 2 + was found to mimic effectively, potentiate and antagonize the stimulatory action of Ca 2 + on myosin light chain kinase (MLCK) and phospholipid-sensitive Ca 2 + -dependent protein kinase (PL-Ca-PK, or protein kinase C). PL-Ca-PK, however, was slightly less sensitive to Cd 2 + regulation than was MLCK. Cd 2 + also biphasically regulates (i.e., stimulation followed by inhibition) phosphorylation, in the homogenates of the rat caudal artery, of myosin light chain and other endogenous proteins catalyzed by MLCK and PL-Ca-PK. The activation by Cd 2 + of MLCK was inhibited by anticalmodulins (e.g., R-24571), whereas the inhibition by a higher Cd 2 + concentration of MLCK and PL-Ca-PK was reversed by thiol agents (e.g., cysteine). The present findings may provide one mechanism underlying the vascular toxicity of Cd 2 + , a major environmental pollutant.