Background: In lymphoproliferative disorders serum β2-microglobulin (β2m) can be useful as a clinical marker. Material and Methods: β2m measurements were carried out with a new assay of Hoffmann-La Roche, which is a one-step solid-phase enzyme immunoassay with competitive inhibition. Sera of 81 healthy subjects, 42 patients with renal failure, 108 patients with monoclonal gammopathies [3 monoclonal gammopathies of undetermined significance (MGUS), 91 multiple myeloma (MM), 14 macroglobulinemia (MG)], and 11 patients with non-Hodgkin lymphoma (NHL) were tested. In addition β2m was determined during follow-up of 29 patients with myeloma and lymphoma. Results: β2m values of normal sera ranged from 1.0 to 3.0 mg/l in 97.5%. Patients with renal malfunction had the highest β2m concentrations (60 mg/l) with significant correlation (ρ < 0.01) to serum creatinine (r=0.45). 57% of the patients with MM and NHL had raised β2m levels when compared to healthy controls. Serum β2m values did not correlate with the serum levels of monoclonal immunoglobulins. Using the myeloma staging system of Durie and Salmon, a strong association of pretreatment serum β2m with advanced stage of disease was found. In stages II and III, β2m levels were significantly higher than in stage I (p < 0.001). Seven patients with smoldering myeloma showed β2m concentrations within the normal range. No association with histologic cell types of myeloma was found. In the follow-up of patients with myeloma, β2m values decreased with response to chemotherapy and were low in stable remission. At relapse very high β2m concentrations were associated with a poor prognosis. Conclusion: Serum β2m appears to be a good prognostic marker in MM independent of the paraprotein concentration. In MM and also in other NHL, β2m determination helps to optimize therapy.