The purpose of this case-control investigation was to investigate the possible association between mild-to-moderate enamel fluorosis and exposure during early childhood to fluoride supplements, fluoride toothpaste, and/or infant formula use in nonfluoridated communities. Analysis was performed on 460 10- to 13-year-old children, born after 1979, who were residents of six nonfluoridated communities in Massachusetts and Connecticut. The fluorosis status of the subjects was determined on the basis of a clinical dental examination using the Fluorosis Risk Index (FRI). Risk factor exposure was ascertained via a mailed questionnaire with a response rate of 90% and a questionnaire reliability of 87%. Logistic regression analyses revealed a moderate association between mild-to-moderate enamel fluorosis on early forming (FRI classification I) enamel surfaces and both fluoride supplement use (odds ratio (OR) = 2.25, 95% confidence interval (CI) 1.08-4.69) and early toothbrushing habits (OR = 2.56, 95% CI 1.34-4.88). There was a strong association between mild-to-moderate fluorosis on later forming (FRI classification II) enamel surfaces and both supplement use (OR = 7.97, 95% CI 2.98-21.33) and early toothbrushing habits (OR = 4.23, 95% CI 1.72-10.41). Infant formula was not found to be associated with fluorosis on either FRI classification I or II surfaces.