The renal afferent arteriole reacts to an elevation in blood pressure with an increase in muscle tone and a decrease in luminal diameter. This effect, known as the myogenic response, is believed to stabilize glomerular filtration and to protect the glomerulus from systolic blood pressure increases, especially in hypertension. To study the mechanisms underlying the myogenic response, we developed a mathematical model of intracellular Ca²⁺ signaling in an afferent arteriole smooth muscle cell. The model represents detailed transmembrane ionic transport, intracellular Ca²⁺ dynamics, the kinetics of myosin light chain phosphorylation, and the mechanical behavior of the cell. It assumes that the myogenic response is initiated by pressure-induced changes in the activity of non-selective cation channels. Our model predicts spontaneous vasomotion at physiological luminal pressures, and KCl- and diltiazem-induced diameter changes comparable to experimental findings. The time-periodic oscillations stem from the dynamic exchange of Ca²⁺ between the cytosol and the sarcoplasmic reticulum, coupled to the stimulation of Ca²⁺-activated potassium (K_Ca) and chloride (Cl_Ca) channels, and the modulation of voltage-activated L-type channels; blocking sarco/endoplasmic reticulum Ca²⁺ pumps or ryanodyne receptors (RyR), K_Ca, Cl_Ca or L-type channels abolishes these oscillations. Our results indicate that the profile of the myogenic response is also strongly dependent upon the conductance of Cl_Ca and L-type channels, as well as the activity of plasmalemmal Ca²⁺ pumps. Furthermore, inhibition of Ca²⁺-activated K+ channels is not necessary to induce myogenic contraction. Lastly, our model suggests that the kinetic behavior of L-type channels results in myogenic kinetics that are substantially faster during constriction than during dilation, consistent with in vitro observations (Loutzenhiser et al., Circ. Res. 90:1316--1324, 2002).