The contractures induced by ouabain (10–3 M), potassium-free solutions, and NaF (10–2 M) in estrogen-dominated rat uterine muscle were prevented or delayed by 0.1% cocaine. In contrast to contractures from ouabain or potassium-free solutions, contractures from NaF were delayed or partly reversed but not prevented. The accompanying downhill ion movements (potassium loss and sodium gain) were partly prevented except when produced by ouabain. Cocaine itself sometimes caused contracture at this concentration but without inducing downhill ion movements. In myometrium from pregnant cats, which required less ouabain (10–6 to 10–5 M) to initiate contracture, 0.03 to 0.07% cocaine opposed both the contractures and the downhill ion movements. Higher cocaine concentrations could not be used as they provoked sustained contractures which were not accompanied by net ion movements. In myometrium from estrogendominated rabbits, both cocaine and procaine in concentrations much lower than 0.1% caused sustained contracture. In concentrations of 0.025 and 0.1%, cocaine caused no downhill ion movements in rabbit myometrium and prevented neither the contractures nor the downhill ion movements initiated by 10–6 to 10–5 M ouabain.Adrenaline (1–10 μg/ml) prevented or reversed contractures of rat uteri from ouabain and potassium-free media and this effect was prevented by nethalide, a beta receptor blocking agent with little direct action. Similar concentrations of adrenaline were less effective against acetylcholine and ATP contractions. 3′5′-Cyclic AMP could not produce relaxation. Sodium fluoride contractures were not prevented or reversed by adrenaline. Adrenaline did not prevent the downhill ion movements accompanying contractures and tended to increase them. Nethalide prevented this effect. The differing actions of adrenaline on sodium and potassium movements and contracture suggested that the systems for sodium and calcium transport were partly independent.Reserpinization of rats did not alter the high threshold of uteri to ouabain, indicating that the cause of the high threshold was not related to endogenous adrenaline or noradrenaline.Neither cocaine nor adrenaline affected the downhill electrolyte shifts induced by cooling to 7 °C, but adrenaline prevented the cold contracture. Neither relaxant affected the electrolyte shifts induced by iodoacetate, but both had slight effects on dinitrophenol electrolyte shifts. There was evidence suggesting that dinitrophenol caused shortening of the unloaded muscles used to study electrolyte shifts.Cupric ion (10–5 to 10–4 M) was found to cause contractures of rat uteri. Cupric ion (10–5 M), after a short exposure of uterine horns, potentiated the subsequent responses of these horns to ouabain, potassium-free solutions, and NaF. Potassium-free solutions and glucose removal tended to potentiate the responses to cupric ion. Cupric ion (10–5 to 10–4 M) did not cause increased potassium loss and in fact diminished the loss of this ion from rat uterine cells; it did appear to increase the uptake of sodium into cells. Its effects on contracture and electrolyte movements were opposed by cocaine. The lack of effect of adrenaline may have been partly related to the very rapid oxidation of this substance in the presence of cupric ion. It was concluded that cupric ion acts similarly but not identically to fluoride and affects Mg- and Na+K-activated membrane ATPase in such a manner as to demonstrate the dissociation of sodium extrusion from potassium uptake.