Primary systemic amyloidosis (AL) is a rare disorder characterized by deposition of a monoclonal immunoglobulin light chain or fragment thereof, resulting in dysfunction of the heart, kidney, liver, or nerves. Despite the use of melphalan, prednisone, colchicine, and dimethyl sulfoxide (DMSO), no improvement in median survival has been reported in prospective randomized studies. We undertook a study of alpha-tocopherol acetate (vitamin E) in the treatment of 16 patients with AL because of its reported benefits in animal models of senile and secondary amyloidosis as well as reported benefit in the treatment of secondary amyloidosis in humans. None of the patients showed any objective regression of their disease. The median survival of the entire group was 19.4 months. This survival is not superior to that reported with other agents used in this disease. We conclude that alpha-tocopherol is not a valuable agent in the treatment of AL.