The two year carcinogenicity of D-xylose was examined in groups of 50 male and 50 female F344 rats at dietary doses of 0% (control), 2.5% and 5%. The doses were selected on the basis of results from a 13-week subchronic toxicity study. Growth suppression and soft feces were observed in male and female rats of the 5% group. However, no significant differences from the controls were noted with regard to clinical signs, mortality and hematological findings. Decrease in absolute weight and increase in relative weight of the brain in males, and decrease of absolute kidney weight in females were observed in the 5% group, but there were no remarkable histopathological changes. A variety of tumors developed in all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any type of neoplastic lesion was found for either sex in the treated groups. Thus, it was concluded that, under the present experimental conditions, D-xylose is not carcinogenic to F344 rats.