Abstract Serum beta-2-microglobulin (B2m) levels were measured in 78 patients with multiple myeloma (MM) and were compared with values for normal individuals and patients with benign monoclonal gammopathies (BMG). Serum B2m levels and values corrected for renal function were significantly higher in patients with MM at time of diagnosis than in normal individuals ( P < 0.001) and were highly correlated with the total body burden of myeloma cells as derived from the staging system of Durie and Salmon. However there were no significant differences between values for BMG and low-mass MM. For patients evaluated following induction chemotherapy, there was also a clear correlation between serum B2m levels and the magnitude of tumor regression or progression ( P < 0.05). During the plateau-phase, serum B2m levels remained very stable and highly correlated with the residual tumor mass ( P < 0.001). It was concluded that (1) B2m was not a reliable marker to distinguish between BMG and low-mass MM and (2) B2m was a valuable marker for assessing initial tumor mass of patients with MM and response to chemotherapy (especially the plateau-phase), above all in patients with urine or low-serum monoclonal component levels.