Immunoglobulin light-chain amyloidosis (AL) is a rare disorder characterized by production of a 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, in death. Although melphalan and prednisone are beneficial in approximately 30% of patients with the disease, many patients fail to respond, and the median survival with this disease remains < 2 years. There is a need for new agents for those patients who fail to respond to melphalan-based chemotherapy. A study was undertaken of high-dose dexamethasone in the treatment of 19 patients with AL because of reports of its benefits in previously untreated patients with amyloidosis and its known activity in the management of multiple myeloma, which has many characteristics in common with AL. In this cohort, 3 of 19 patients showed an objective organ response of the disease. The median survival of the entire group was 11.2 months. We conclude that high-dose dexamethasone therapy is of occasional benefit in patients previously treated for amyloidosis. Combining dexamethasone with other therapies may increase the response rate.