Twenty-five patients with multiple myeloma received bone marrow grafts (n = 24) or peripheral blood stem cells (n = 1) from twin donors. The outcome was compared in a case-matched analysis to 125 patients who underwent autologous transplantation, and 125 who underwent allogeneic transplantation. Seventeen patients (68%) receiving twin transplants entered complete remission, which was not significantly different from that of autologous (48%) or allogeneic (58%) transplants. The median overall and progression-free survival for the twins was 73 and 72 months, respectively. The overall survival tended to be better (73 vs 44 months) and the progression-free survival was significantly better (72 vs 25 months) than with autologous transplantation and both were significantly better than with allogeneic transplantation. Three of 17 patients who entered complete remission following transplantation had relapsed at follow-up. This relapse rate was significantly lower than following autologous transplantation and similar to the relapse rate with allogeneic transplantation. Only two twins died of transplant-related toxicity. Six further patients died of progressive or relapsing disease. Syngeneic transplantation in multiple myeloma appears to be the treatment of choice if a twin donor is available. A lower relapse risk than in autotransplantation may be due to reinfusion of malignant cells in some patients treated with this modality or to the presence of a graft-versus-myeloma effect in some syngeneic transplants.