The Behring Nephelometer is a new automatic analyzer designed for the measurement of specific proteins. The authors evaluated the nephelometer in the determination of M proteins as compared with immunodiffusion and cellulose acetate electrophoresis. In addition, the effects of sample dilution and antigen excess on the nephelometric measurement of M proteins were studied in 24 patient samples containing a single monoclonal IgG, IgA, or IgM M component. Immunodiffusion cannot be recommended for the determination of M proteins. Nephelometry and protein electrophoresis gave similar results with few exceptions. Sera with immunoglobulin monomer-oligomer pairs involve difficulties in serum electrophoresis. In certain cases, special care must be taken to adjust the nephelometric measurement of the M protein to the most accurate part of the calibration curve. All in all, the new Behring Nephelometer proved precise and reliable in M protein determination without risk of antigen excess.