Heavy metals have been shown to exert immunotoxic effects on humoral immunity. To ascertain the mechanisms by which these immunotoxic effects are exerted, the effects of CdCl2 and HgCl2 on the biology of murine B-lymphocytes were studied. It was shown that CdCl2 aand HgCl2 inhibited B-cell RNA and DNA synthesis. The IC50 (the concentration required to inhibit a specific B-cell function by 50%) for CdCl2 was 30 μM for RNA synthesis and DNA synthesis. The IC50 for HgCl2 was 50 and 120 nM for RNA and DNA synthesis, respectively. Cell cycle analysis revealed that B-cells were arrested throughout the cell cycle with CdCl2 and HgCl2. The inhibitory effects exerted by CdCl2 were rapid, inhibiting RNA synthesis within 2 h of activation. Differentiation to Ig secretion was inhibited by CdCl2 and HgCl2 in culture and there appeared to be selective effects on specific Ig isotypes. IgG3 production was most sensitive to inhibition by CdCl2 and HgCl2 followed by IgG1 and IgG2b and then IgM and IgG2a. Changes in the expression of B-cell surface antigens induced by LPS were also influenced by CdCl2. LPS-induced increases in class II MHC expression was inhibited by CdCl2, as was the constitutive expression of class I MHC antigen. A summary of the IC50 for CdCl2 are presented. In summary, both CdCl2 and HgCl2 exert early, inhibitory effects on B-cell activation. This is manifested by the inhibition of RNA, DNA and antibody synthesis. However, selective effects on the production of specific Ig isotypes by these metals may influence the ability of B-cells to mount effective immune responses to pathogens.