In a large number of patients with multiple myeloma, chemotherapy is the only therapeutic option. During recent years, major effort has been put into immunotherapeutic approaches for this malignancy. In this study, wild-type (wt) myeloma cells (5x10(5)) were injected subcutaneously into Balb/c mice. CD40L-transfected myeloma cells (5x10(5)) were subsequently injected intratumorally into the established (>100 mm(3)) wt tumor nodules. Overall survival and tumor growth were measured. Out of eight animals receiving wt tumor cells, one died prior to the formation of a solid tumor nodule. Following the CD40L-transfected myeloma cell injection, stable complete remission at day 60 with all the animals surviving resulted. On day 60, a re-challenge was performed with wt myeloma cells. No tumor growth was observed after 120 days out of seven remaining animals, one died. Intratumoral injection of CD40L-transfected myeloma cells induces complete tumor remission and long lasting immunity against tumor recurrence.