(1) Evidence has been presented suggesting that progesterone pretreatment in vivo increases the rate of leakage of potassium from rabbit uterine segments into a saline–bicarbonate medium.(2) Various types of evidence indicate that in uterine tissues, the loss of potassium from cells into potassium-free solutions is increased during the contractile actions of drugs. There was no clear-cut concomitant increase in tissue sodium concentrations. The results tend to confirm previous findings indicating that increases in potassium (but not in sodium) permeability are associated with contraction of smooth muscle.(3) Epinephrine effects on potassium loss occurred only in uteri which contracted in response to epinephrine. Norepinephrine, but not iproterenol, had a similar effect. Dibenamine, alone, decreased potassium loss and partly blocked the effects of epinephrine. Direct measurement of glycogen content suggested that these findings were not related to a glycogenolytic action of the epinephrine. Rather, the effect of epinephrine to increase potassium loss seemed to be closely related to its contractile action. In long-term experiments, both epinephrine and calcium slowed the rate of K loss and of water and sodium gain. This effect also was absent in uterine tissues which were not contracted by epinephrine.