The early stages of weight loss are associated with a reduction in blood pressure, and the mechanisms mediating this reduction remain unclear. Platelet free calcium levels, [Ca2+]i, have been reported to be elevated in essential hypertension and to decrease with pharmacological treatment of the hypertension. In the current study, 18 obese subjects had measurements of blood pressure, forearm blood flow, forearm vascular resistance, and both basal platelet [Ca2+]i and [Ca2+]i responses to vasopressin during 12 weeks on a very low calorie (3,360 kJ, or 800 kcal) diet. Weight reduction was associated with reduction in mean arterial blood pressure at 3-4 weeks. There were associated reductions in forearm vascular resistance and platelet [Ca2+]i as well as increases in forearm blood flow at 3-4 weeks of the diet. Increased forearm blood flow was correlated with weight loss. Vasopressin-induced platelet [Ca2+]i responses increased, which correlated with the reduction in mean arterial pressure at 7-8 weeks of weight loss. Assuming that platelet [Ca2+]i metabolism reflects vascular smooth muscle cell [Ca2+]i metabolism, the data suggest that blood pressure reduction after weight loss may be related to reduced vascular smooth muscle cell [Ca2+]i. The reason for the increased vasopressin-induced [Ca2+]i after weight reduction is unclear.