Lovastatin has been used with increasing frequency over the past few years to reduce serum cholesterol. The onset of muscle weakness, one of the most serious side effects of long-term treatment with the drug, constitutes a contraindication to the continuation of therapy and commonly occurs in patients who are also receiving gemfibrozil or cyclosporine. We report the clinical and pathologic findings in a patient treated for hypercholesterolemia with lovastatin and gemfibrozil who developed a rapidly progressive necrotizing myopathy. A 57-year-old woman with hyperlipidemia, treated with lovastatin and gemfibrozil, was admitted to the hospital for evaluation of muscular weakness in her legs and neck. Neurologic examination revealed severe proximal muscle weakness involving both upper and lower extremities as well as proximal muscle tenderness and areflexia in the lower limbs. A biopsy of the quadriceps muscle showed multiple foci of mononuclear cell infiltration with myophagocytosis and slight variation in the size and shape of muscle fibers. Electron microscopy of the affected fibers showed accumulations of subsarcolemmal autophagic lysosomes. The patient’s condition dramatically improved after discontinuation of lovastatin-gemfibrozil therapy.