Primary systemic amyloidosis is the disorder that results from the deposition of insoluble immunoglobulin light chain fragments. Patients seen within 30 days of diagnosis have a median survival of 13 months. Patients treated with melphalan and prednisone have a median survival of 17 months. There is a need for new therapies. A prospective study was undertaken of high-dose dexamethasone in the treatment of 25 patients with previously untreated primary systemic amyloidosis. Treatment was similar to that given to patients with multiple myeloma. In this cohort, three patients showed objective regression with organ-specific improvement of the disease. The median survival of the entire group was 13.8 months. High-dose dexamethasone is of occasional benefit in patients with amyloidosis but does not appear to be superior to melphalan and prednisone chemotherapy.