Previous studies have shown that fluoride (F) administered concomitantly with sucrose in drinking water, in the diet, or alone is an effective cariostatic agent. The purpose of the present study was to determine the minimum concentration of F co-crystallized with sugar that may be used to prevent dental caries in rats subjected to a severe cariogenic challenge. Desalivated Sprague-Dawley rats, infected with Streptococcus sobrinus, were placed in a König-Höfer programmed feeder. The rats received 17 meals daily for 21 days as follows: group (1) sucrose and sterile distilled water (s.d.w.); (2) sucrose and 1 part/10(6) F-water; (3) 1 part/10(6) F-sucrose and s.d.w.; (4) 4 parts/10(6) F-sucrose and s.d.w.; (5) 8 parts/10(6) F-sucrose and s.d.w.; (6) sucrose and 10 parts/10(6) F-water. Essential nutrition was administered by gavage. At death, blood was collected from each animal and one-half of the lower jaw was sonicated in 0.9% saline solution for microbial assessment and F analysis. Keyes smooth-surface and sulcal caries scores were significantly lower in the groups that received 10 parts/10(6) F-water and 8 parts/10(6) F-sucrose than in all other groups. The F concentration in the jaw suspension and plasma were significantly higher in the 10 parts/10(6) F-water and the 8 parts/10(6) F-sucrose groups than in all other groups. The total cultivable flora and Strep. sobrinus populations were lowest in F groups but this did not reach statistical significance. It is concluded that 8 parts/10(6) F co-crystallized with sucrose reduces the cariogenic potential of sugar as effectively as 10 parts/10(6) F in water, that is as little as 1 part/10(6) in sucrose has a significant effect, and that this cariostatic action is related to the amount of F in the oral environment.