This study was designed to evaluate beta-adrenergic responsiveness as assessed by the generation of cyclic AMP after the subcutaneous administration of epinephrine in 31 subjects: normal controls, patients with chronic renal insufficiency, hemodynamically stable patients on chronic acetate dialysis and hemodynamically unstable patients with acetate intolerance on chronic bicarbonate dialysis. As compared with controls, only unstable patients on bicarbonate dialysis presented impaired beta-responsiveness, which, in turn, was acutely reduced only after acetate but not bicarbonate dialysis. Our results show that acetate dialysis impairs the beta-adrenergic responsiveness and that the observed beta-hyporesponsiveness in unstable patients with acetate intolerance may represent part of a broader spectrum of autonomic dysfunction which may develop in some patients on chronic hemodialysis.