Specimens of buccal mucosa obtained at autopsy from 216 patients were examined for histopathologic alterations. Atrophic oral epithelium was found in thirty cases. A retrospective study of the hospital records revealed that thirteen of these latter patients had been on a cancer chemotherapeutic regimen prior to death. There was a significantly higher incidence of atrophy in the chemotherapy group (p less than 0.001) than in control patients. These findings, as well as the expected inherent susceptibility of rapidly replicating oral epithelial cells to metabolic inhibitors, suggest a causal relationship between oral atrophy and the administration of cancer chemotherapeutic agents. This atrophy may therefore represent a preliminary stage of mucosal alteration that ultimately progresses to the clinical sequelae of stomatitis and oral ulcerations frequently encountered during cancer chemotherapy. Some alternative mechanisms are also discussed.