The aim of this investigation was to study the effect of an in vitro acquired, stable, fluoride-resistant strain of Streptococcus mutans on dental caries in rats. Three groups (P0, P5 and P10) of SPF Osborne-Mendel rats were inoculated with the fluoride-sensitive S. mutans C180-2. Three other groups (FR0, FR5 and FR10) were inoculated with cultures of the fluoride-resistant S. mutans C180-2FR. Diet SSP 20/5 and tap water (less than 0.2 ppm fluoride) were available ad libitum to all groups. The drinking water of groups P5 and FR5 was supplemented with 5 mg F-/1 and the drinking water of groups P10 and FR10 with 10 mg F-/1. At the end of the caries experiment (days 58/59) there were no significant differences in the percentages and in the numbers of S. mutans in the total maxillary plaques of groups P0 to P10 and of groups FR0 to FR10, respectively. The fluoride tolerance of S. mutans cells re-isolated from rats, inoculated with the fluoride-sensitive strain, showed an unstable decrease compared to before inoculation. S. mutans cells re-isolated from rats, inoculated with the fluoride-resistant strain, showed both unstable and stable adaptation towards fluoride sensitivity. The animals superinfected with the fluoride-resistant strain developed less dentinal/fissure caries. Fluoride given in the drinking water at concentrations of 5 and 10 mg/l was effective in reducing caries irrespective of whether the animals were superinfected with the fluoride-sensitive or the fluoride-resistant strain.(ABSTRACT TRUNCATED AT 250 WORDS)