To clarify the effect of histamine on antibody production, histamine was injected intravenously into DNP-KLH immunized C3H/HeN female mice. The number of anti-DNP plaque-forming splenic cells decreased in immunized and histamine-injected mice. Decreased PFC responses similarly occurred in recipient mice into which Lyt-2.1 T cells obtained from histamine-injected mice were transferred before immunization. The effect of histamine is not due to inhibition on plaque formation. The results indicated that histamine induced the augmentation of suppressor T cell (Ts) function and caused the decrease of antibody production in histamine-injected mice. The maximum activity of Ts in recipient mice was obtained from mice injected with histamine 3 days before the cell transfer. The suppressive activity of histamine was not antigen specific because Ts was induced in histamine-injected, nonimmunized mice. The treatment of histamine type 2 (H2) agonist showed decreased PFC responses in the mouse as well as histamine did. When mice were treated with an H2 antagonist followed by histamine, antibody production was not reduced. The above results indicated that histamine seemed to regulate antibody production through H2 receptors on lymphocyte membranes.