Owing to lack of progress with standard chemotherapy and the presence of a dose response effect for alkylating agents, autotransplantation is performed with increasing frequency for multiple myeloma (MM). However, sustained relapse-free survival is still infrequent. We studied 94 patients who had relapsed following autotransplantation, in order to evaluate the efficacy of further therapy. Post-transplant salvage treatment consisted of either standard dose therapy (53) or transplantation with an intensive preparative regimen (with autograft support in 31 and allogeneic transplantation in 10). Complete remission (CR) rate, event-free and overall survival were assessed and prognostic variables identified in a multivariate regression analysis. With a median follow-up of 11 months, the projected overall survival at 18 months for all patients is 59%. A multivariate analysis identified pre-salvage beta-2-microglobulin (B2M) < or = 2.5 mg/l (P = 0.0002) and late relapse after the preceding transplant ( > 12 months; (P = 0.02) as independent significant favorable variables for overall survival. By combining pre-salvage B2M and the time to relapse, 2 risk groups of patients could be identified with significantly different overall survival: those with at least one favorable variable had a projected survival at 18 months of 79%, compared to 38% for patients with no favorable variable. Transplantation performed as primary salvage therapy was associated with a significantly prolonged survival (P = 0.009), although this may be more a reflection of the way salvage therapy was selected.