There have been a number of reports on the improvement of concomitant autoimmune disease (AID) after autologous hematopoietic stem cell transplantation (SCT) performed for hematologic malignancy. However, in some cases of hematologic malignancy with AID, exacerbation of AID after autologous SCT has been reported. We have treated 27 adults with multiple myeloma with single or tandem autologous SCT. After peripheral blood stem cells were collected and stored without CD34+ cell selection or T-cell depletion, all patients received melphalan (200 mg/m2) as a conditioning regimen. In 2 patients with a history of AID (one with rheumatoid arthritis [RA] and the other with bullous pemphigoid [BP]) and in 1 patient with Sjögren syndrome, AID recurred 7 to 12 months after autologous SCT. The RA and BP were in durable remission before SCT, and no Sjögren syndrome-related disease activity was clinically documented at the time of SCT. No progression of the myeloma was observed when the AIDs recurred. The patients required systemic steroid therapy for their AID, and successful control of the disease was achieved. Our experience suggests that autologous SCT with unmanipulated stem cells for myeloma is unlikely to cure preexisting AID; rather, the AID may worsen. Transplantation physicians should be aware of this possible complication.