In smooth muscle it is generally accepted that at the level of the contractile apparatus regulation is achieved by activating a dormant state in the presence of Ca<sup>2+</sup>. This event initiates the contractile process which is manifest by an increased cross-bridge cycling rate and the development of tension, or in biochemical terms, by an increase in the activation by actin of the Mg<sup>2+</sup>-ATPase activity of myosin. A controversy exists, however, on the identity of the activator, and this review considers the two proposed possibilities. One theory is based on the phosphorylation and dephosphorylation of the 20,000 dalton molecular weight myosin light chains. It is assumed that in the phosphorylated state the Mg<sup>2+</sup>-ATPase activity of myosin can be activated by actin whereas dephosphorylated myosin cannot be activated by actin. Phosphorylation of myosin, and hence the activation of the contractile apparatus, is achieved by a myosin light chain kinase, and it has been shown that the calcium dependence of the phosphorylation reaction resides with one of the two components of this enzyme, namely calmodulin. Inactivation of the contractile apparatus is brought about by a second enzyme, the myosin light chain phosphatase. There is considerable experimental evidence in support of the phosphorylation theory and it appears that it must be at least a part of the regulatory system. However, it cannot be concluded that phosphorylation-dephosphorylation of myosin is the sole regulatory mechanism, and recent results have indicated that additional factors may be involved. The second theory to account for the activation of the contractile apparatus is not based on the phosphorylation of the myosin molecule and is thought to be due to a system called leiotonin. This system, composed of two subunits leiotonin A and C, is thought to be associated with the thin filaments. Its mode of action has not been established.