We compared cases with outflow tract defects (N = 126) with controls representative of the same birth cohort (N = 679). Infants with clinically recognized syndromes were excluded. Daily total maternal folate intake of > or =245 microg was inversely related to risk of cardiac outflow tract defects among those with transposition (odds ratio estimates: 0.65, 0.78, and 0.76 with increasing quartile of daily folate intake), but positively related among those with normally related vessels (corresponding odds ratio estimates: 1.18, 1.59, and 1.68). This difference disappeared when maternal intake of supplemental folic acid of > or =400 microg compared with <400 microg was considered, excluding dietary intake [odds ratio (OR) = 1.04; 95% confidence interval (CI) = 0.5-2.2 for infants with transposition, and OR = 0.91; 95% CI = 0.5-1.8 for those without transposition of the great arteries].