Susceptibility to infection is widely recognized as the major cause of morbidity and mortality in patients with CLL and MM. The present study was designed to investigate the serum bactericidal (SBA) and serum opsonic activities (SOA) in 12 CLL and 12 MM patients, and results were compared to 20 normals. SBA and SOA were measured by a new radiometric assay. SBA was found to be normal in 11 patients with CLL and in all 12 patients with MM. In contrast, SOA was significantly lower in 11 out of 12 patients with CLL. Ten of twelve patients with MM also had significantly lower SOA compared to those of controls. No correlation was detected between the serum immunoglobulin and complement levels of the patients or between the degree of the opsonic defect and the incidence of infection. In mixture experiments, untreated normal serum partially corrected the opsonic activity of CLL and MM serum. The results suggest the presence of a possible inhibitor in the serum of patients with two well-known B-lymphocyte-derived disorders.