Rats subjected to inhalation of 3500 ppm o-xylene for 6 weeks were found to increase their body-weight at a lower rate than did the controls, despite an increased food and fluid intake, and to develop hepatic enlargement. Post mortem studies revealed no other abnormality. The distribution of the hepatocellular nuclei according to size was, however, modified. The proportion of large nuclei was higher in the test animals than in the controls, and the number of cells per unit area was lower, as a sign of cellular hypertrophy. Electron microscopic studies revealed a loss of glycogen, and increase of rough and smooth endoplasmic reticulum and of peroxisomes. These changes which are typical of the adaptational phase of poisoning may be connected with the induction of the mixed function oxidase system. Enzyme histochemical and ultrastructural studies also revealed a slight hepatocellular damage.