PURPOSE: Although weight reduction generally lowers blood pressure, it is unclear whether the response is due to concurrent dietary changes or to reduced body mass itself. In this study, the independent effects of energy restriction and weight reduction were examined prospectively in 24 obese, hypertensive, normoglycemic women whose dietary intake was tightly controlled. SUBJECTS AND METHODS: Sodium, potassium, and calcium intake, the polyunsaturated/saturated fat ratio, and the proportional composition of carbohydrate, fat, and protein were constant throughout the 5-month protocol. Hemodynamic and neuroendocrine status was evaluated in four 10-day hospital phases: two prior to weight loss (energy balance and then 800-kcal intake), and two after an average loss of 13 kg to normal body weight (800 kcal and then return to energy balance). RESULTS: Fasting serum insulin, triiodothyronine:reverse triiodothyronine ratio, resting metabolic rate, and heart rate declined, and sodium and potassium balances were negative during energy restriction. Catecholamines, renin, aldosterone, plasma volume, cardiac output, and blood pressure showed no consistent response to changes in energy intake. By contrast, weight reduction independently lowered blood pressure, plasma volume, cardiac output, and plasma renin activity. Body fat pattern remained unchanged. CONCLUSION: These results demonstrate that weight loss has a blood pressure-lowering effect that is distinct from energy restriction and that is related to changes in blood volume and cardiac output.