The effects of oleandrin, a cardiac glycoside, were tested on the cardiovascular system of anesthetized dogs with an intact circulation. Oleandrin, administered intravenously, at dosages of 0.01 (Group I), 0.02 (Group II), and 0.05 (Group III) mg/kg, did not affect the mean heart rate significantly in any of the groups of dogs studied. Results were most consistent with 0.05 mg/kg of oleandrin in Group III producing a significant increase in aortic systolic, aortic mean, and left ventricular peak pressures. Oleandrin increased the inotropic state of the heart in all groups of dogs to some extent and the magnitude of change was directly related to the amount of the drug injected. The increased contractility was expressed as a rise in the indices of max dp/dt and max dp/dt/IP, and as a decrease in t-dp/dt. In Group III, with 0.05 mg/kg of oleandrin, left ventricular contractility increased by over 50% as judged from these indices. Oleandrin, in the majority of the dogs, shifted the pressure-velocity curves upward and to the right, increasing both VCE and Vmax. In Group III the increase in Vmax was 32%. The results indicate that oleandrin in the intact, normal dog produced responses that are both qualitatively and quantitatively similar to those seen with the better known cardiac glycosides.