Prevalence of asthma increases with increasing dichlorodiphenyldichloroethylene (DDE) levels. However, the effect of early-life exposure, the fundamental window of exposure, is unknown. We assessed the association between prenatal DDE and other organochlorine compounds, and atopy and asthma during infancy. All women presenting for antenatal care in Menorca (Spain) over 12 months starting in mid-1997 were invited to take part in a longitudinal study; 482 children were subsequently enrolled, and 468 (97.1%) provided complete outcome data up to the fourth year of study. Prenatal exposure of organochlorine compounds was measured in cord serum in 405 (83%) children. Asthma was defined on the basis of wheezing at 4 years of age, persistent wheezing, or doctor-diagnosed asthma. We measured specific immunoglobulin-E (IgE) against house dust mite, cat, and grass in sera extracted at 4 years of age. DDE (median = 1.03 ng/mL) was detected in all children, as well as hexachlorobenzene (0.68 ng/mL) and polychlorobiphenyls (0.69 ng/mL). Wheezing at 4 years of age increased with DDE concentration, particularly at the highest quartile [9% in the lowest quartile (< 0.57 ng/mL) vs. 19% in the highest quartile (1.90 ng/mL); relative risk = 2.63 (95% confidence interval 1.19-4.69), adjusting for maternal asthma, breast-feeding, education, social class, or other organochlorines]. The association was not modified by IgE sensitization and occurred with the same strength among nonatopic subjects and among those with persistent wheezing or diagnosed asthma. DDE was not associated with atopy alone. Prenatal exposure to DDE residues may contribute to development of asthma.