Paradoxical hypotension during rapid infusion of plasma protein fraction (PPF) has been attributed to yasodilation by bradykinin in PPF. This study employed a canine, controlled right heart bypass preparation to assess changes in systemic vascular resistance and venous capacitance during infusion of PPF and other possibly vasoactive mediators. Plasma protein fraction caused consistent vasodilation, whereas purified human albumin did not. This vasodilation could be ascribed entirely to acetate, present in PPF as a buffer. Bradykinin in PPF had no effect during venous infusion. Acetate is used widely as a buffer in intravenous and dialysate solutions. Its vasoactive properties must be recognized when such solutions are administered to patients with limited capacity to compensate for sudden vasodilation.