BACKGROUND: There are few therapeutic options for patients with multiple myeloma who relapse after autologous or allogeneic stem cell transplantation, or for patients who are refractory to conventional chemotherapy and not eligible for salvage high-dose therapy. Thalidomide, a potent antiangiogenic agent, has been suggested as an effective salvage therapy in refractory multiple myeloma. The aim of this study was to evaluate the efficacy and tolerance of thalidomide as a single agent as multicenter trial in Korea. METHOD: From February 2001 to September 2002, 28 patients from 4 institutions were included. At start of treatment, all patients had active disease and 17 (61%) had received at least one autologous transplantation. RESULTS: The serum or urine levels of paraprotein were reduced by at least 90 percent in two patients, at least 50 percent in three patients, and at least 25 percent in two patients; for a total response rate of 25 percent. 13 patients had stable disease and 8 patients had progressed. At least half of the patients had mild or moderate constipation and fatigue. More severe adverse effects were infrequent. CONCLUSION: This study confirms that thalidomide is an effective and safe agent in patients with relapsed or refractory multiple myeloma.