HgCl2, CuSO4, SnCl2, SnCl4 or sodium lauryl sulphate (SLS) were openly applied to rat oral mucosa for 1 min, followed 6 h later by histologic examination of the tissue response. Granulocytes were the predominant inflammatory cells and no lymphocytic infiltration could be seen with any of the substances tested. Irritant threshold levels were defined histologically for each of the substances. CuSO4 was found to be non-irritant at all concentrations. The addition of non-irritant concentrations of SLS lowered the threshold levels for HgCl2 and SnCl2, but CuSO4/SLS was non-irritant at all concentrations tested. Preapplication to the mucosa of SLS at non-irritant concentrations gave results with HgCl2, SnCl2 and CuSO4 similar to those with SLS added to the metal salt solutions. Lesions of allergic contact type could not be induced in the oral mucosa to any of the metal salt preparations.