Cocaine-induced contractures of rabbit uterine segments were analyzed. Similar responses were produced by other local anesthetics, but potency in producing contractures was unrelated to that in producing local anesthesia. Contractures were not produced by potentiation of endogenous catecholamines or by any mechanism related to stimulation of α-adrenergic receptors or oxytocin receptors. Receptors for serotonin and acetylcholine were also not involved. Depolarization of the uterine muscle cells prevented cocaine-induced contractures. They were calcium-dependent and disappeared more rapidly than responses to acetylcholine or noradrenaline in a calcium-free medium. They were restored both by strontium and by calcium, but more slowly than were acetylcholine responses. It is proposed that cocaine causes labilization of calcium loosely bound in the membrane in rabbit uterine segments and that this leads to contracture.