Prevalence of mutans streptococci (MS) and the effect of selected variables, including the early childhood use of antibiotics on the oral colonization of MS, were studied among 353, 5- to 12-year-old African-American children using a cross-sectional study. MS prevalence was estimated using pooled plaque and stimulated saliva samples (spatula). Data on antibiotic use and other potential determinants of oral colonization of MS were obtained using a self-administered questionnaire. Antibiotic data were validated using health records of subjects. MS prevalence (92%, 95% Confidence Interval [CI] = 89-95%) was associated with dental caries (Odds Ratio [OR] = 2.5, 95% CI = 1.3-6.2), age (Chi for trend = 4.3, P = 0.04), increased frequency of sweet consumption (Chi for trend = 5.1, P = 0.02), and increased number of teeth in the mouth (unit OR = 1.3, 95% CI = 1.1-1.6). Higher MS levels were associated with higher number of decayed teeth (P < 0.0001), and also, with having the mother as the primary caregiver during the second year of life (P = 0.02). Furthermore, children who took antibiotics during early childhood and those who lived in the same household with many others during the second year of life had a higher MS prevalence than those who did not (OR = 8.3, 95% CI = 2.0-35.0; unit OR = 1.5, 95% CI = 1.03-2.2, respectively). It is unclear why those exposed to antibiotics during the "window of infectivity" of MS exhibit a higher MS prevalence. Antibiotic-related oral ecological changes (i.e, lower levels of S. sanguis) and environmental changes (i.e., frequent exposure to sugar through most pediatric antibiotic preparations) may make the oral cavity more favorable for initial MS colonization.