The contraction of vertebrate smooth muscle, like all other types of muscle is the result of a cyclic interaction of the proteins myosin and actin in a process coupled to the hydrolysis of ATP. The regulation of smooth muscle contraction is very complex involving several distinct regulatory systems. Because of the great importance of the regulation of smooth muscle contraction, particularly in relation to vascular disease, the various components of these regulatory systems must be identified and the interactions which produce overall regulation must be defined. The primary regulatory system in smooth muscle appears to be myosin based with dephosphorylation of myosin causing relaxation. More evidence has been accumulating that an actin-linked system may further modulate the force producing interaction of myosin with actin. A likely candidate for an actin binding regulatory protein is the recently identified protein, caldesmon. The inhibitory function of caldesmon will be studied in detail. Its binding to actin and other proteins in the contractile apparatus will be quantitated. Finally, the interplay of myosin based and actin based regulatory systems in smooth muscle will be examined. Other potential regulatory proteins from smooth muscle may also be studied.