Separan AP-273, a polydisperse, high molecular weight (105-107dalton range), anionic polyacrylamide, demonstrates polymer drag reduction (Toms effect) in the flows of several substances including blood. That is, under appropriate conditions, pipe flow can be increased markedly for a given pressure gradient, sometimes threefold or more, by nanomolar concentrations of linear macropolymers. The effect of intact and degraded Separan was tested in the open-chest, anesthetized rat, and left ventricular and carotid pressures, aortic blood flow (electromagnetic flow probe on ascending aorta), and the electrocardiogram were recorded. The results indicate that aortic flow, which in control animals was about half the flow reported for conscious rats, increases markedly after injection of Separan. The effect on blood pressure after an initial fall was variable, but the slope of arterial diastolic pressure was consistently steepened. Electrocardiographic changes were unremarkable except for a slow decline in heart rate. Although secondary reflexes undoubtedly influenced the results, the primary mechanism of the polymer appears to involve a reduced resistance to flow. The results are compatible with the proposal that the Toms effect, or some variant of it, is operative in vivo under favorable conditions. If this view is correct, then Separan and two other chemically different macropolymers with similar hemodynamic effects and physical attributes, i.e., linearity and molecular lengths approaching 100 μn, might be prototypes of a novel category of cardiovascular drugs.