The acute hemodynamic effects of an intravenously (i.v.) injected poly(ethylene oxide), Polyox WSR N-60K (dose 50 mg/kg), were studied in the open-chest rat anesthetized with sodium pentobarbital. The injectate is one of four drag-reducing polymers known to augment in vitro blood flow under a constant pressure gradient; the others are an anionic polyacrylamide (Separan), a rhamnogalactogalacturonan (RGGu), and a deoxyribonucleic acid (calf thymus DNA). RGGu and Separan both augment cardiac output in the rat. Aortic blood flow, measured with an electromagnetic flow probe mounted on the ascending aorta, increased immediately after administration of the polymer and remained above control flow for at least 1 h. A small sustained decrease in heart rate (HR) was associated with a prolongation of systole. Ventricular and arterial blood pressures increased progressively over the 2-h postinjection period. Total peripheral resistance (TPR) initially decreased but then increased continuously throughout the experimental period, eventually surpassing the control value. Although the in vivo effects of Polyox differ from those of RGGu and Separan, the effects of the three macromolecules on aortic flow and TPR are similar at least in the first hour. Because the three substances are chemically dissimilar, these results further support the hypothesis that the primary mechanism responsible for the hemodynamic changes caused by some drag-reducing polymers--apparently limited to those with molecular lengths approaching 100 microns--is physical in nature.