The aim of this study was to determine whether there is a gender-related difference in the morbidity and mortality of infants of diabetic mothers. We also wanted to identify risk factors associated with adverse pregnancy outcome, and create a perinatal morbidity index. We performed a retrospective review of 107 women whose pregnancies were singleton and complicated by diabetes. The subjects were divided according to the gender of the infant. The morbidity, mortality and confounding variables between the two groups were compared. Logistic regression analysis was used to identify the independent factors associated with an adverse pregnancy outcome. The male group (n = 62) had higher morbidity than the female group (n = 45). This was due to a higher incidence of hypoglycemia (relative risk = 3.9, 95% CI 1.2-12.5, p = 0.011) and need to stay in the neonatal intensive care unit 2 or more days (relative risk = 1.8, 95% CI 1.1-2.9, p = 0.015). There was one female stillbirth due to an episode of ketoacidosis in the mother. Male gender (relative risk = 1.8, 95% CI 1.2-2.7, p = 0.002) was one of three independent predictors of poor outcome. There is a male disadvantage in infants of diabetic mothers with regards to perinatal morbidity. Advanced White's classification, male gender, and third trimester mean glucose > or = 110 mg% identify the pregnancies at risk for diabetes-related morbidity.