Primary systemic amyloidosis (AL) is a rare disorder characterized by production of an aberrant monoclonal light chain. This insoluble light chain, or a fragment thereof, deposits in tissues as amyloid and results in disruption of organ function and, ultimately, death. Although melphalan and prednisone were reported to benefit subsets of patients with the disease, many patients showed no benefit; the median survival with the disease is ∼2 years. There is a need to develop new agents for patients who fail to respond to a trial of cytotoxic chemotherapy. A study was undertaken of interferon alfa-2 in the treatment of 15 patients with AL because of its reported benefits in the induction and maintenance therapy for patients with multiple myeloma, a disease that has many characteristics in common with AL. None of the patients showed any objective regression of their disease; the median survival of the entire group was 26.3 months. This survival is not superior to that reported with other agents used for this disease. We conclude that interferon alpha-2 is not a valuable agent in the treatment of AL. © 1993 Wiley-Liss, Inc.