The effects of CL 115,347, a novel prostaglandin E2 (PGE2) congener, on a variety of hemodynamic variables were examined in conscious spontaneously hypertensive rats. Within minutes of topical administration (0.03, 0.3, or 3.0 mg/kg), a dose-dependent decrease in mean arterial blood pressure (MABP) was observed. One hour following drug application, a stable, dose-related hypotensive effect was still apparent, with MABP from 18 to 33 mm Hg lower than control, predose values. Quantitation of blood flow using radioactive microspheres indicated that a significant increase in stroke volume and cardiac output (3.0 mg/kg only), as well as a reduction in total peripheral resistance, was associated with the administration of CL 115,347. Further analysis of regional blood flow implied that vasodilation in specific vascular beds may contribute importantly to the antihypertensive activity of this compound.