Arterial contractility in response to various drugs was studied in media designed to alter ionic gradients of sodium and potassium across the cell membrane. Tissues were analyzed to determine the effects of these procedures on tissue electrolytes and to demonstrate any correlation between tissue electrolytes and response.It was found that the contractile responses progressively decreased in sodium-free media, disappearing in 2 to 2½ hours. A decrease in external potassium, initially caused a potentiation of response. Thereafter, a decreased response was manifested, yet contractility remained even after 7 to 8 hours in potassium free medium. Increased external potassium caused an increase in response.There was no correlation between the content of sodium and potassium and response in potassium-free solutions, but in sodium-free solutions a positive correlation between contractility and potassium content existed.Chloride appeared to exist in 2 fractions, a diffusible fraction, and a more tightly bound fraction. Calculation of the ECFV based on the bound chloride yielded values which otherwise would have been absurd.Sodium appeared to be distributed in 3 fractions; diffusible and extracellular, not diffusible over the duration of our experiments and slowly diffusible and presumably intracellular, the latter fraction being possibly capable of cation exchange.Evidence obtained does not suggest that the sodium gradient, per se, is responsible for contractility. The concentration of intracellular potassium does not influence contractility directly. However, the potassium gradient may in part determine vascular muscle contractility.