Monoclonal antibodies (MAbs) 17.13 and 63.12 exhibit characteristic reactivity patterns in normal stratified squamous epithelium, as well as highly sensitive and specific altered reactivity patterns in squamous cell carcinoma. The purpose of this study was to critically evaluate the patterns of reactivity of MAbs 17.13 and 63.12 in 43 biopsies of clinical oral leukoplakia or erythroleukoplakia with microscopic diagnoses of hyperkeratosis or epithelial dysplasia. Altered carcinoma-like reactivity patterns were seen in 72% of hyperkeratoses and in all cases of epithelial dysplasia, but varied in the level of epithelial strata exhibiting altered reactivity. Increased frequency of altered reactivity within the epithelial strata was associated with the presence, but not the grade of, epithelial dysplasia, as well as with the presence, intensity; and pattern of submucosal inflammation. The results of this study suggest that altered reactivity patterns of MAb 17.13 are associated with epithelial dysplasia and may be of assistance in detecting precancerous changes in hyperkeratoses before morphologically identifiable epithelial dysplasia. The association of submucosal inflammation with altered MAbs 17.13 and 63.12 reactivity may indicate either a decrease in specificity of these antibodies for precancerous change or an increased significance of inflammation in precancerous lesions.