Abstract Female Sprague-Dawley rats had 6 weeks of 0 (control), 75 or 100 parts/10 6 sodium fluoride in their drinking water. Whole mandibular incisors were removed, fixed, demineralized and sections prepared for light-microscopic morphometric analysis of dose-related alterations in enamel protein retention. Other rats given 0 and 75 parts/10 6 only (control and experimental groups) were used for autoradiographic evaluation of alterations in enamel protein removal. 35S-methionine was applied directly over secretory ameloblasts at the end of the fifth week of fluoride exposure. Incisors were removed either 5 or 7 days later and processed for autoradiographic analysis. The results indicated: (1) extended retention of enamel proteins in fluoride-exposed maturation enamel as well as reduced enamel protein synthesis and/or secretion in the secretory stage; (2) negative linear correlation between extended enamel protein retention and reduced enamel protein secretion among groups; and (3) repression of enamel protein removal. The data are also consistent with the concept that the fluoride effect is multifactorial.