Twenty male volunteers, average age 24 years, participated in this study. Specimens were obtained by enamel biopsy using 5 microliters of 0.5 M HClO4 for 30 s. Using a regression curve, comparisons of fluoride concentrations were made at different depths. The fluoride concentrations (mean +/- SE) at a depth of 5 microns were highest in the distobuccal (1698 +/- 136), high in the mesiobuccal (1343 +/- 122), low in the distolingual (1119 +/- 107), and lowest in the mesiolingual sites (819 +/- 78). Of the interior enamels (> or = 10 microns in depth), the distobuccal site (1330 +/- 88 parts/10(6) F at 10 microns) had a higher-concentration than all other sites. The fluoride profiles were steepest to shallowest in the order: distobuccal, mesiobuccal, distolingual and mesiolingual. There were no correlations between the enamel fluoride concentrations and the fluoride concentration in parotid saliva. It was concluded that in vivo fluoride profiles of maxillary first molars reflect the wear of the tooth surface with age and the condition of dental plaque deposition, and, to some extent, the site-specific distribution of saliva between buccal and lingual surfaces.