Histopathological studies in rats and dogs have indicated that hexachlorobenzene (HCB) has immunotoxic properties. Rats exposed to low doses of HCB showed proliferation of high endothelial venules in lymph nodes and accumulation of macrophages in lung alveoli, while lymphoid hyperplasia of the splenic white pulp occurred at higher doses. In dogs, HCB administration produced hyperplasia of lymphoid tissue in the stomach. Functional assessment showed that cell-mediated immunity (delayed-type hypersensitivity response), and humoral immunity (primary and secondary antibody responses to tetanus toxoid) even more, were enhanced in the rat, while macrophage function was unaltered. Stimulation of these immune responses occurred at a dietary level as low as 4 mg/kg HCB following combined pre- and postnatal exposure; at this dose, conventional parameters for hepatotoxicity were unaltered. The developing immune system of the rat therefore seems particularly vulnerable to HCB. In contrast to the immune stimulation observed in the rat, HCB has been reported to suppress the humoral and cell-mediated immunity as well as the resistance to protozoan (malaria and leishmania) infections and to tumour-cell challenges in the mouse; effects have been observed at a dietary HCB level of 5 mg/kg. However, recent data have suggested that HCB has some potential to stimulate the immune system of the mouse also, since increased resistance was shown to a viral infection and to a tumour-cell challenge. Strain differences or the presence of immunosuppressive contaminants in the HCB preparations used do not seem to explain these apparently contrasting results. Although further studies are needed to resolve this discrepancy, current data provide strong enough evidence to classify HCB as a potent immunotoxic chemical.