The purpose of this long-term study was to investigate disturbances in enamel mineralization associated with low, but relatively constant, plasma fluoride levels produced by constant infusion or with fluctuating plasma fluoride levels caused by drinking fluoridated water. Weanling rats were raised for 8 weeks on low-fluoride food and water containing 0, 10, 25 or 60 ppm fluoride. Two other groups received their fluoride from subcutaneously implanted minipumps. The daily fluoride exposure of the two latter groups was 0.14 and 0.32 mg/day, while that of the 10-ppm water group averaged 0.41 mg/day. The terminal plasma fluoride levels of the 10-ppm water group was 3.0 µM, and of the two minipump groups were 1.5 and 3.1 µM, respectively. The mandibular incisor enamel in each of these groups showed microradiographic evidence of fluorotic changes which was most severe in the minipump group with an average plasma fluoride concentration of 3.1 µM. The disturbances in enamel mineralization were most apparent in the 25- and 60-ppm water groups. There were no differences among the groups for plasma calcium concentrations. The findings suggest that: (1) enamel fluorosis has a time component in addition to a concentration or intake component; (2) the rat incisor is a better model for human enamel fluorosis than heretofore believed, and (3) disorders in calcium homeostasis are not necessarily involved in enamel fluorosis.