Stem cell transplantation was introduced as a new therapeutic modality for amyloidosis. The purpose of the current study was to determine the feasibility and toxicity of stem cell transplantation for amyloidosis in a cooperative group setting in which most participating institutions would have limited experience in managing the disorder. A total of 30 patients with biopsy-proven amyloidosis shown to be immunoglobulin light-chain type were enrolled on this trial. The protocol required mobilization of a minimum of 6 × 108 mononuclear cells/kg or 5 × 106 CD34+ cells/kg ideal body weight. These targets had to be achieved within seven collections. Patients with advanced hepatic, renal, or cardiac failure were excluded. End points included objective response rate and overall survival. The secondary end point of the protocol was nonhematologic toxicity. Accrual to the study was faster than expected. The overall response rate (hematologic and organ) was 64%, with three treatment-related deaths. Another patient died before day 30 of sudden cardiac death not treatment related. The median follow-up of surviving patients is 30.3 months. Median survival has not been reached. Stem cell transplantation for selected patients with amyloidosis is feasible in a cooperative group setting. A multicenter phase 3 trial of high-dose therapy is indicated.