It has previously been shown that HgCl2 injected subcutaneously in Brown Norway (BN) rats (RT1n) induces an autoimmune syndrome with glomerulonephritis and epiphenomena in various tissues. We have, with monoclonal antibodies, investigated cellular infiltrates of the oral mucosa in Hg-treated BN rats. Our results show an infiltration of CD45RB- T cells and ED1+ monocytes. In comparison with experimental contact hypersensitivity to 2,4-dinitrofluorobenzene, we found a low expression of RT1B and RT1D. No B cells were found. SD rats (RT1(1/u], treated identically, did not respond. Intense reactions with dense mononuclear cell infiltrates were seen in BN rats injected with HgCl2 and subsequently challenged in the oral mucosa with low doses of HgCl2 in acetone/olive oil. In contrast, no significant infiltrates appeared in BN rats epicutaneously painted with HgCl2 followed by oral challenge. Thus, the route by which Hg is introduced to the immune system seems to be decisive for the appearance of oral lesions in BN rats. The findings indicate that low-dose exposure to Hg can bring about epiphenomena resulting in an increased T cell dependent reactivity of the oral mucosa to Hg in genetically predisposed individuals.