The aim of this study was to evaluate the effect of milk supplemented with probiotic bacteria and fluoride on caries development and general health in preschool children. Children 1-5 years of age (n = 248) attending 14 day care centres with 27 units in northern Sweden entered the study. The centres were randomly assigned to two parallel groups: children in the intervention group were served 150 ml milk supplemented with Lactobacillus rhamnosus LB21 (10(7) CFU/ml) and 2.5 mg fluoride per litre for lunch while the control group received standard milk. The double-blind intervention lasted for 21 months (weekdays) and data were collected through clinical examinations and questionnaires. The primary outcome was caries increment and secondary outcomes were measures of general health. The dropout rate was 25%. The mean baseline caries experience was 0.5 dmfs in the intervention units and 0.6 in the control units and after 21 months 0.9 and 2.2 (p < 0.05). The number of days with sick leave was similar in both groups but the children of the intervention units displayed 60% fewer days with antibiotic therapy (mean 1.9 vs. 4.7 days) and 50% less days with otitis media (0.5 vs. 1.0) (p > 0.05). In children who had participated during the whole 21-month intervention, fewer days with otitis media were reported (0.4 vs. 1.3 days, p < 0.05). No serious side effects were reported. It is concluded that daily consumption of milk containing probiotic bacteria and fluoride reduced caries in preschool children with a prevented fraction of 75%. Additional beneficial health effects were evident.