Morphological and cytochemical studies on the squirrel monkey have been made after maintaining the sujects on pure distilled water and fluoridated distilled water for 18 months with the objective of determining the effect of fluoride on the activity of some hydrolytic and oxidative enzymes in the kidney, liver and nervous system. Daily water intake by individual animals was measured over the final 10 months of the animal's exposure to 0,1 and 5 ppm fluoride. Water consumption was considerably higher in the animals on higher fluoride intake. Whereas the nervous system remained totally unaffected by this experimental procedure, the liver showed a slightly enhanced acivity of Krebs citric acid cycle enzymes. The kidneys, however, showed significant cytochemical changes, especially in the animals on 5 ppm fluoride intake in their drinking water. In these animals, the glomeruli showed an increase in the activity of acid phosphatase and the enzymes belonging to the citric acid cycle and the pentose shunt, whereas lactate dehydrogenase, a resentative of the anaerobic glyoclytic pathway, remained unchanged or only slightly changed. These observations suggest that fluoride in concentrations as low as 5 ppm interferes to some extent with the intracellular metabolism of the excretory system.