The effects of whole cells of three different 0 serotypes of Vibrio anguillarum on the murine immune response were studied. The addition of different doses (1-100 p,g/ml) of V. anguillarum cells, as well as Salmonella typhimurium lipopolysaccharide, markedly increased the incorporation of [3H]thymidine into in vitro cultured spleen cells of C57BL/6 mice. All three serotype strains of V. anguillarum were able to induce the mitogenic effect at 10 p,g/ml and 100 p,g/m1, but serotype I strains were more potent than the others. Since pretreatment of spleen cells with rabbit anti-mouse thymocyte antiserum did not affect the mitogenic activity of V. anguillarum, Vibrio cells may be a B-lymphocyte mitogen.When sheep or horse erythrocytes and Vibrio cells were injected intraperitoneally into ddY mice, Vibrio cells exhibited an enhancing effect on antibody response in vivo, regardless of the different serotypes. Vibrio cells, when injected intraperitoneally into mice before the antigen, markedly suppressed the antibody response. Several days after the injection of Vibrio cells, these mice showed an enhanced carbon clearance activity. Acid phosphatase activity in their peritoneal cells was also augmented, suggesting that Vibrio cells activated macrophages in the mice.Vibrio anguillarum, a gram-negative and halophilic marine bacterium, causes vibriosis in fish, both wild and cultured (I, 17,25); this is one of the most serious diseases affecting different kinds of fish (25).We previously reported that V. anguillarum has antitumor activity against Ehrlich carcinoma cells in mice, which may be mediated by immune lymphocytes of the host (24). Although numerous physiological, biochemical and serological studies on V. anguillarum have been carried out (1,15,17,21,25), no report has been published on the effect of the bacteria on the host immune systems.In this paper, we describe the following effects of whole V. anguillarum cells of three different 0 serotypes: a) a mitogenic effect on splenocytes (3[H]thymidine uptake), b) an adjuvant effect on antibody response to xenogeneic erythrocyte antigen, c) stimulation of the carbon clearance system, and d) enhancement of acid phosphatase activity in peritoneal exudate cells.929