In a prospective study in 65 untreated patients with early-stage B-cell chronic lymphocytic leukemia (B-CLL), serum monoclonal Igs (moIg) were evidenced in 80% of cases by a sensitive immunoblotting procedure. These low-abundance moIg were generally undetectable by immunoelectrophoresis and individual sera often contained several of them. Their kappa/lambda ratio was close to 1 instead of 2.8 for the lymphocyte surface Igs. A monoclonal IgM of the same light-chain type as the lymphocyte surface IgM was found in 26 sera only. The distribution of the heavy-chain classes and subclasses and light-chain types of the serum moIg was similar to those observed in aging (with a higher incidence and no correlation with age in B-CLL) and conditions with defective T-cell functions. Using a specific filter affinity- transfer assay, rheumatoid factors were detected in 58.5% of sera. However, homogeneous anti-IgG antibodies corresponding to a monoclonal IgM of the same light-chain type as the surface IgM were found in 10 patients only. These data suggest that the majority of discrete serum moIg in B-CLL are not secretion products of the leukemic clones and likely result from the immunodeficiency state inherent in the disease.