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 infant formula, fluoride toothpaste, and/or fluoride supplements. Analysis was performed on 401 residents of fluoridated communities in Connecticut, who were 12-16 years old and born prior to 1980. The case and control subjects for this study were selected on the basis of a clinical examination given in 1991. Subject fluorosis status was determined using the Fluorosis Risk Index. Risk factor exposure was ascertained via a mailed questionnaire with a response rate of 89% and a questionnaire reliability of 87%. Logistic regression analyses, which adjusted for confounding variables, revealed that mild-to-moderate enamel fluorosis on early forming (Fluorosis Risk Index (FRI) classification I) enamel surfaces was strongly associated with both milk-based (odds ratio (OR) = 3.34, 95% confidence interval (CI) 1.38-8.07) and soy-based (OR = 7.16, 95% CI 1.35-37.89) infant formula use, as well as with frequent brushing (OR = 2.80, 95% CI 1.15-6.81). A very strong association was observed with inappropriate fluoride supplement use (OR = 23.74, 95% CI 3.43-164.30). Respectively similar associations were observed between mild-to-moderate enamel fluorosis on later forming (FRI classification II) enamel surfaces and frequent brushing and fluoride supplement use, but not with infant formula use.