The periodontal conditions and the subgingival microflora of children, adolescents and young adults (8-28 years old) with Down syndrome were investigated in the present cross-sectional study and compared with those of healthy individuals and subjects with cerebral palsy. Seventy Down syndrome patients, 121 age-matched healthy individuals and 76 patients with cerebral palsy participated in the present study. Full-mouth recordings of clinical parameters (probing depth, probing attachment level, bleeding on probing, hygiene index) and the community periodontal index of treatment needs were assessed and subgingival plaque samples were taken from the Ramfjord teeth and analysed for 14 species using "checkerboard" DNA-DNA hybridization. Clinical indices of periodontal inflammation and treatment needs were statistically significant higher among Down syndrome patients compared with the other two groups (ANOVA, p=0.000). Important periodontal pathogens colonize these subjects earlier and at higher levels (chi-squared test, p=0.000). Down syndrome patients display more severe periodontal destruction earlier, and heavier colonization with periodontal pathogens compared with age-matched healthy individuals and patients with cerebral palsy.