Carbon tetrachloride exposure in mice induces a serum associated immunosuppressive factor(s) that inhibits T-cell dependent immune responses. The objective of the present studies was to characterize the immunomodulatory activity of serum isolated from carbon tetrachloride-treated mice on T-cell independent humoral immune responses. Direct addition of serum isolated from carbon tetrachloride-treated mice (500 mg/kg/day for 7 days) to naive spleen cell cultures enhanced the antibody forming cell response to lipopolysaccharide as compared to serum from naive or vehicle-treated mice. Enhanced antibody forming cell responses were also observed when spleen cells isolated from carbon tetrachloride-treated mice were sensitized with this T-cell independent antigen 24 h, but not 48 h or 72 h, following exposure of mice to one dose of 500 or 1000 mg/kg of carbon tetrachloride. Additionally, spleen weight and spleen:body weight ratio were increased in mice sensitized in vivo with sheep red blood cells 24 h after exposure to a single dose of carbon tetrachloride (500 or 1000 mg/kg) as compared to naive antigen sensitized mice and mice sensitized 48 and 72 h after exposure to carbon tetrachloride. Fluorescence activated cell sorting analysis indicated that daily exposure to carbon tetrachloride (250 or 500 mg/kg for 7 days) increased the percentage of B-cells in the spleen without altering the number of TH-cell or TC/S cell populations. Taken together, these results suggest that exposure to carbon tetrachloride induces a serum borne factor(s) that produces a modest increase in the functional activity and number of B-cells in the spleen.