Despite the increased amounts of serum immumoglobulins (Ig) in multiple myeloma, the percentage of bone marrow-dependent (B) cells carrying surface Ig in the peripheral blood compartment were decreased, when compared with that in control patients with polyclonal gammopathy or with that in normals (5 plus or minus 2% in patients with multiple myeloma and 19 plus or minus 5% or 22 plus or minus 7% in controls). Most circulating B cells in patients with multiple myeloma were shown to carry individually specific idiotypic Ig. The monoclonal idiotypic nature of the surface Ig was shown by using antiserums raised against the monoclonal Ig. The idiotypic antiserum was capable of actively binding to and stimulating the idiotypic lymphocytes to divide in vitro. Commercial anti-Ig antiserums raised against normal Ig did not bind to the myeloma lymphocytes. After chemotherapy, lymphocytes carrying the idiotypic Ig decreased in numbers, and this correlated with other variables of clinical improvements. Its role in the pathogenesis of myeloma and its importance for diagnosis and follow-up of patients with myeloma are discussed.