To assess the consequences of hypercalcemia on systemic and renal bemodynamics, vasoactive hormones, and water and electrolyte excretion in intact, conscious mongrel dogs, measurements in 10 dogs receiving 100 mg/kg calcium gluconate and 10,000 U/kg vitamin D daily for 2 weeks were compared with measurements made in 10 tune-control dogs not receiving calcium or vitamin D. Hypercalcemia induced by dietary supplementation with calcium and vitamin D resulted in profoundly reduced glomerular filtration rate (40 vs 78 ml/min in controls;p< 0.005), estimated renal plasma flow (145 vs 267 ml/min in controls;p< 0.005), and renal blood flow (254 vs 441 ml/min in controls;p< 0.005). Renal resistance was significantly increased in the hypercalcemic dogs (0.57 ± 0.07 vs 0.28 ± 0.01 mm Hg/ml/min;p< 0.005). Hypercalcemia also resulted in increased fractional excretion of water (4.8 vs 1.4% in controls;p< 0.005), sodium (1.4 vs 0.6% in controls;p< 0.005), calcium (1.7 vs 0.7% in controls;p< 0.01), and magnesium (10.2 vs 4.1% in controls;p< 0.005). Systolic blood pressure (160 vs 172 mm Hg in controls;p< 0.05) and stroke volume were lower (0.024 vs 0.036 L/beat in controls;p< 0.005) in hypercalcemic dogs, presumably because of the diuresis, while total peripheral resistance was higher (36 vs 31 mm Hg/L/min;p< 0.05) in controls. Magnesium levels were significantly lower in the experimental group (1.3 vs 1.7 mg/dl in controls;p< 0.0005). Aldosterone levels, plasma renin activity, and urinary prostaglandin excretion were not significantly affected. These results suggest that hypercalcemia induced by chronic dietary supplementation increases total peripheral resistance and renal vascular resistance, which may be due to the direct effects of increased calcium ions or to indirect effects on other vasoactive humoral systems including reductions in magnesium ions.