We studied the interaction of lipopolysaccharide (LPS) and concanavalin A (Con A) with regard to IgM and IgG production in in vitro cultures of human peripheral blood lymphocytes (PBL). In our system LPS alone over a wide range of concentrations did not stimulate detectable IgM or IgG production, while Con A at optimal (6 microgram/ml) and suboptimal (0.6 microgram/ml) mitogenic concentrations induced synthesis of small amounts of Ig. A marked enhancing effect was present when both Con A and LPS were added to the cultures. The different doses of LPS has similar effects on both classes of Ig, and typical dose-response curves were obtained. To evaluate the cellular basis of this synergism, the effect on cell proliferation was studied under identical experimental conditions in normal subjects and patients with X-linked agammaglobulinaemia (X-LA). Parallel cultures were set up after monocyte depletion by adherence on Petri dishes. On day 3, increasing doses of LPS were associated with progressive decreases in 3H-thymidine (3H-TdR) incorporation. Similar results were obtained with normal lymphocytes and those from X-LA patients. Monocyte depletion did not substantially alter the lymphocyte response pattern. The preferential induction of helper activities, either directly by helper stimulation or indirectly by suppressor inhibition, is suggested as a possible mechanism of the interaction observed.