The response of ameloblast to long term (3 weeks) exposure to fluoride was examined in continuously erupting mandibular incisors of pregnancy rats as compared to control rats receiving a similar diet (Teklad L-356) but no sodium fluoride in there drinking water. Rats were started on water containing 0 ppm, 100 ppm, 200 ppm, and 300 ppm NaF at the beginning of pregnancy. To examine on the ultrastructural changes of the ameloblast, electron microscopy was used. The results indicated that rat incisors expressed two major changes in normal amelogenesis that could be attributed to chronic fluoride treatment. The fluoride produces marked alteration in the fine structure of ameloblast from teeth of young rats, such as large confluent distensions of the endoplasmic reticulum and swelling of isolated mitochondria, in particular on the morphology of the rough-surfaced endoplasmic reticulum. A graded series of alterations to these organelles were produced, and the severity of the changes would seem to be dependent on dose and time. This experimental data suggested that exposure prolonged of animal to high level of fluoride appears to induce morphological changes in the normal appositional growth and initial mineralization of enamel created during amelogenesis.