Measurement of serum free-light chains (FLCs) was performed using a recently developed immunoassay in 180 healthy individuals, 16 patients with multiple myeloma, and each 1 patient with Waldenström's macroglobulinemia, primary amyloidosis, or MGUS (monoclonal gammopathy of undetermined significance) to evaluate the clinical relevance of FLCs in the diagnosis and disease monitoring. Serum FLC levels of each patient were elevated compared with the levels of healthy individuals. The changes in FLC levels after treatment and at the time of relapse occurred earlier than those in serum immunoglobulin levels due to the short half-life of FLCs. Serum FLC levels were elevated in patients with Bence Jones type myeloma in spite of negative urinary immunoelectrophoresis. The serum FLC assay is a sensitive and useful tool for the diagnosis and monitoring of multiple myeloma and other B-cell proliferative disorders.