OBJECTIVES Smoking has been linked to small cognitive, achievement, and behavioral deficits but has not been associated with more severe cognitive impairments. This investigation evaluated the relationship between maternal smoking during pregnancy and idiopathic mental retardation (MR). METHODS Data on maternal smoking during pregnancy were obtained during face-to-face interviews with the mothers of 221 children with idiopathic MR and the mothers of 400 children attending public school. All children had been born in the five-county metropolitan Atlanta area in 1975 or 1976 and were living in the area when they were 10 years of age. We used exposure odds ratios (ORs) to assess the relationship between maternal smoking and MR, controlling for sex, maternal age at delivery, race, maternal education, economic status, parity, and alcohol use. RESULTS Maternal smoking during pregnancy was associated with slightly more than a 50% increase in the prevalence of idiopathic MR (adjusted OR, 1.6; 95% confidence interval, 1.0-2.4), and children whose mothers smoked at least one pack a day during pregnancy had more than a 75% increase in the occurrence of idiopathic MR (OR, 1.9; 95% confidence interval, 1.0-3.4). This increase was neither accounted for by other sociodemographic risk factors for MR nor explained by an increase in the prevalence of low birth weight among the children of smokers. CONCLUSIONS Our data suggest that maternal smoking may be a preventable cause of mental retardation.