We carried out HLA-matched related (n = 16) and unrelated (n = 17) hematopoietic cell transplantation (HCT) in 33 patients with relapsed and refractory mantle cell lymphoma after nonmyeloablative conditioning with fludarabine and 2 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Fourteen patients had failed high-dose autologous HCT. Of the 33 patients studied, 31 had stable engraftment, whereas 2 patients experienced nonfatal graft rejections. The incidences of acute grades II, III, and IV, and chronic graft-versus-host disease (GVHD) were 27%, 17%, 13%, and 64%, respectively. The overall response rate in the 20 patients with measurable disease at the time of HCT was 85% (n = 17; 75% complete remissions [CR] and 10% partial remissions [PR]), whereas 3 patients had progressive disease. Only one of the 17 patients who responded and none of the 13 who received transplants in CR had disease relapse with a median follow-up of 24.6 months. Relapse and nonrelapse mortalities were 9% and 24%, respectively, at 2 years. The Kaplan-Meier probabilities of overall and disease-free survivals at 2 years were 65% and 60%, respectively. Allogeneic HCT after nonmyeloablative conditioning is a promising salvage strategy for patients with relapsed and refractory mantle cell lymphoma. The high response and low relapse rates with this approach suggest that mantle cell lymphoma is susceptible to graft-versus-tumor responses.