The study of cellular Ca 2+ exchange in smooth muscle has been severely limited by extensive extracellular Ga 2+ binding. This problem was solved by using La 3+ to trap Ca 2+ inside the cells while displacing extracellular bound Ca 2+ . It was then shown that cytoplasmic Ca 2+ could be raised by Ca 2+ influx during high K+ depolarization, Na+ elimination and high pH. Ca 2+ influx was inhibited by other multivalent cations, local anaesthetics and low pH. In the rabbit aortae norepinephrine and angiotensin increase cytoplasmic Ca 2+ by release from intracellular membrane surfaces. In this same smooth muscle relaxation is brought about by intracellular Ca 2+ binding. Evidence from vascular, uterine and intestinal smooth muscle demonstrates that the large transmembrane Ca 2+ gradient depends on cellular [ATP] but not on the Na+ gradient. ATP depletion abolishes the Ca 2+ gradient by increasing Ca 2+ influx.