The distribution of the major VL subgroups (V-lambda I, V-lambda II, V-lambda III, V-lambda IV, V-lambda VI, and V-lambda VIII) among lambda-type immunoglobulins (Igs) in normal serum was determined by a sandwich enzymelinked immunosorbent assay (ELISA) using a panel of murine anti-human V-lambda-subgroupspecific monoclonal antibodies (MoAbs) end appropriate reference standard proteins. The mean concentration of lambda I, lambda II, lambda III, lambda IV, lambda VI, and lambda VIII Igs in serum specimens obtained from 23 adults was 2158, 162, 1958, 264, 225, and 169 mu g/mL and represented 44, 3, 40, 5, 5, and 3% of the total Ig lambda population, respectively. The low percentage of lambda II Igs in normal serum was in marked contrast to the similar to 40% incidence of this V-lambda subgroup found among lambda-type Bence Jones proteins and monoclonal serum Igs obtained from patients with multiple myeloma and AL amyloidosis, or similar to 60% in Waldenstrom's macroglobulinemia. The non-random expresson of the VlambdaII subgroup in these diseases implies a relationship between V-lambda-gene usage and plasma cell, as well as certain types of lymphocytic dyscrasias. (C) 1994 Wiley-Liss, Inc.