We studied the risk for specific birth defects among infants of mothers with gestational and chronic diabetes using data collected by the Spanish Collaborative Study of Congenital Malformations (ECEMC). For the years 1976 to 1985, we identified 10,087 infants with malformations and 9,994 control infants; 155 of the case infants and 89 of the controls were born to diabetic mothers. The crude odds ratio for any minor or major defect and insulin-treated diabetes was 5.5 (95% CI = 1.2, 24.8), and for major malformations it was 8.7 (95% CI = 1.8, 34.7). The risk for defects involving the central nervous system (CNS), skeletal system and cardiovascular system were significantly increased. Infants of non-insulin-treated diabetic mothers were 2.9 times more likely to have a major congenital birth defect (95% CI = 1.2, 7.2). The crude odds ratio for any major or minor defect and mothers with gestational diabetes requiring insulin was 1.9 (95% CI = 1.1, 3.4). Similar risk was observed for major defects (OR = 1.9, 95% CI = 1.0, 3.7). These results suggest that infants of insulin-treated diabetic mothers have an increased risk of developing malformations of the CNS, cardiovascular system and skeletal system. We also found an increased risk for specific defect categories among infants of mothers with gestational diabetes treated with insulin.