Airway smooth muscle cell contraction is regulated by changes in intracellular Ca²⁺ concentration ([Ca²⁺]_i) and the responsiveness of the airway smooth muscle cell to this Ca²⁺. The mechanism controlling [Ca²⁺]_i primarily involves agonist-induced release of Ca²⁺ from internal stores to generate Ca²⁺ oscillations. The extent of contraction correlates with the persistence and frequency of these Ca²⁺ oscillations. The maintenance of the Ca²⁺ oscillations requires Ca²⁺ influx, but membrane depolarization appears to have a minor role in initiating or sustaining contraction. Contraction also requires agonist-induced Ca²⁺ sensitization, which is mediated mainly by decreases in myosin light-chain phosphatase activity. Although it is not clear if airway hyperresponsiveness associated with asthma results from the specific modulation of these Ca²⁺-based regulatory mechanisms, bronchodilators relax airways by both attenuating the Ca²⁺ oscillations and by decreasing the Ca²⁺ sensitivity.