The aim of the present study was to compare gene expression of the major differentiation-specific keratins in oral epithelium: keratins 4, 13, 1, and 10. Previous studies have shown that the dominant keratins in normal buccal epithelium are K4 and K13, with minor populations of cells showing K1 and K10 expression; herein, we have further examined expression of these keratins at the mRNA level. Six biopsies from normal buccal mucosa were immunohistochemically stained for keratin proteins by means of monoclonal antibodies to K4, K13, K1, and K10. Adjacent sections were processed for mRNA by nonisotopic in situ hybridization, using specific riboprobes labeled with digoxigenin. Proteins for K4 and K13 were expressed suprabasally throughout buccal epithelium, with columns of cells staining additionally for K1 and K10. In situ hybridization revealed a comparable pattern of mRNA distribution for K4 and K13, with expression restricted to parabasal and lower prickle cells. Transcripts for K1 and K10 were present in basal, parabasal, and lower prickle layers, showing a much wider expression than that of their proteins. This study has shown that in buccal epithelium, there is extensive mRNA expression of the" inappropriate" differentiation-specific keratins, despite minimal protein expression. This suggests that K1 and K10 are regulated at the post-transcriptional level, so that they may be expressed adaptively as proteins. The findings will form a useful baseline for the study of these keratins in pathologically altered oral epithelia as well as in nonkeratinized epithelia from extra-oral sites.