A kinetic model was proposed to simulate an isometric contraction curve in smooth muscle on the basis of the myosin phosphorylation hypothesis. The Ca2+-calmodulin-dependent activation of myosin light-chain kinase and the phosphorylation-dephosphorylation reaction of myosin were mathematically treated. Solving the kinetic equations at a steady state, we could calculate the relationship between the Ca2+ concentration and the myosin phosphorylation. Assuming that two-head-phosphorylated myosin has an actin-activated Mg2+-ATPase activity and that this state corresponds to an active state, we computed the time courses of the myosin phosphorylation and the active state for various Ca2+ transients. The time course of the active state was converted into that of isometric tension by use of Sandow's model composed of a contractile element and a series elastic component. The model could simulate not only the isometric contraction curves for any given Ca2+ transient but also the following experimental results: the calmodulin-dependent shift of the Ca2+ sensitivity of isometric tension observed in skinned muscle fibers, the disagreement between the Ca2+ sensitivity of myosin phosphorylation and that of isometric tension at a steady state, and the disagreement between the time course of myosin phosphorylation and that of isometric tension development.