Chemoprevention with retinoic acid (RA) derivatives may reduce the incidence of transformation of potentially malignant oral lesions, and help prevent development of second primary tumours in the upper aerodigestive tract. At present, little is known about the mechanisms by which RA derivatives modify cell proliferation and differentiation. RA interacts with two classes of nuclear receptors: the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We have used immunohistology to localise these receptors on normal epidermis and oral mucosa. The distribution of RAR and RXR suggests that RA may exert complex growth regulatory effects on oral mucosa. Increased levels of RAR and RXR, together with alterations in the patterns of expression of these receptors, were seen when dysplastic and malignant epithelia were compared to normal oral mucosa. These findings suggest that expression of RAR and RXR receptors is modulated in epithelia showing altered growth regulation.