The influence of the synthetic corticosteroid dexamethasone sodium phosphate (DEXA) upon mouse B cells was studied. This was done by in vivo treatment of mice with a single or multiple injection of DEXA, and by culturing murine spleen cells and bone marrow cells in vitro in the presence of different concentrations of DEXA. The effect of DEXA on the B-cell compartment was assayed by polyclonal stimulation of the B cells by Escherichia coli lipopolysaccharide (LPS) in vitro and subsequent measurement of the Ig-secreting cell response in the protein A plaque assay. DEXA treatment could greatly reduce the number of B cells in the spleen, but the bone marrow B-cell compartment was quite resistant to DEXA. The in vitro LPS-induced IgM response of the residual B cells from both spleen and bone marrow and their capacity to switch from IgM to IgG and IgA secretion were not affected. These data indicate that DEXA can decrease the total number of B cells but not the functional capacity of the residual LPS-reactive B cells. This was confirmed at the clonal level by limiting dilution culture experiments. The contrasting effects of DEXA on splenic and bone marrow B cells was also found when the cells were exposed to the drug in vitro. It was found that 10(-8) M DEXA in vitro reduced the response of splenic B cells to LPS by more than 80%, while a similar reduction of the response by bone marrow B cells required a 1000-fold higher concentration.