In ten patients with multiple myeloma (MM), serum beta-2-microglobulin (B2M) levels were monitored in order to clarify the influence of alpha interferon (IFN) administration. Despite decreases in M-protein and the absence of renal dysfunction, the levels of serum B2M were sustained above those prior to melphalan-prednisolone and IFN therapy in seven patients with MM for six months. Serum B2M did not increase in ten patients with MM treated only by melphalan-prednisolone. Furthermore, serum B2M levels in a patient who achieved a complete response were sustained above her prior level and returned to normal after cession of IFN therapy. Our study suggests that the serum B2M level is increased by treatment with IFN, and does not prove the condition of the disease.