Renal tubular acidosis in renal transplant recipients usually is asymptomatic and subclinical. The authors report a case of severe renal tubular acidosis manifested as muscle weakness in a renal transplant recipient. The patient received a renal transplant 30 months ago and had a history of successive episodes of acute rejection during the past 2 months. On admission, arterial blood (arterial blood pH, 7.11; pco(2), 12.8 mm Hg; and bicarbonate, 4 mEq/L [4 mmol/L]) and urine gas analysis were compatible with distal renal tubular acidosis. The graft biopsy findings showed superimposed acute rejection on chronic allograft nephropathy, and immunohistochemical staining and electron microscopic findings showed the reduced immunoactivity of H(+)ATPase pump and anion exchanger 1. The patient was treated successfully with intravenous bicarbonate and oral steroid pulse therapy. This finding suggests that rejection-related renal tubular acidosis should be considered a cause of severely affected metabolic acidosis in renal transplant recipients.