The effect of defined increments of weight loss on hemodynamics has been investigated in conscious, unrestrained, spontaneously obese rats. Obese rats were subjected to a calorically restricted diet and were used for experimentation on achieving a 10, 20, or 30% reduction in body weight. After monitoring resting blood pressure and heart rate, radioactive microspheres were infused for determination of blood flow distribution. Of 10 organs sample, only heart, liver, kidneys, and 2 adipose tissue depots exhibited significant decreases in weight associated with body weight reduction. Mean arterial blood pressure remained unchanged, while stroke volume, left ventricular work, and cardiac output decreased significantly. Blood flow decreased to kidneys, testes, and adipose tissue through a 30% reduction in body weight, but the fractional distribution of cardiac output decreased only to adipose tissue. Therefore the large decreases in renal and adipose tissue blood flow during weight reduction may contribute to the associated decrease in cardiac output. Of those vascular beds examined, however, both absolute and relative blood flow decreased only to adipose tissue, thus denoting the influence of fat mass on hemodynamics during obesity.