Dentifrices, two containing sodium lauryl sulphate (SLS) and one containing stearylethoxylate as surfactant, were gently rubbed on the mucosal surface of the medial wall of cheek pouches in adult male Syrian golden hamsters. Four daily applications were performed. On the fifth day, the animals were sacrificed and cheek pouch mucosal tissue was routinely processed for light microscopy. After applications of SLS containing dentifrices, the epithelium showed consistently prominent structural changes, especially hyperkeratinization, including ortho and para-keratinization, acanthosis with widening of the intercellular spaces, and varying degrees of basal hyperplasia. Identical morphological changes were also observed after application of a paste containing only SLS as an agent. In contrast, after application of the stearylethoxylate containing dentifrice, as well as a paste containing only stearylethoxylate as an agent, the epithelium remained essentially identical to the epithelium of cheek pouches treated with sterile saline, and to the nontreated cheek pouches. From these results, we may conclude that SLS is the agent responsible for the striking changes in the epithelial structure. The specific cytological effects of SLS on the epithelial cells remain to be further studied. Interestingly, application of SLS provides a useful system for the rapid production of acanthosis and hyperkeratinization in the stratified squamous epithelium of the hamster cheek pouch.