Maternal illness and drug/medication use (prescription, over-the-counter, and illicit) during pregnancy might be related to childhood leukemia risk. These issues were evaluated using data (1995-2002) from the Northern California Childhood Leukemia Study. The authors selected 365 children under age 15 years who had been diagnosed with incident leukemia and birth certificate controls who were matched to them on age, sex, Hispanic ethnicity, and maternal race. Data on maternal illnesses and drug use from before pregnancy through breastfeeding were obtained by interview with the biologic mother and were analyzed by conditional logistic regression. Maternal history of influenza/pneumonia was associated with a statistically significant increased risk of acute lymphoblastic leukemia (ALL) in the offspring (odds ratio (OR) = 1.89, 95% confidence interval (CI): 1.24, 2.89), although the risk was nonsignificant for common ALL (OR = 1.41, 95% CI: 0.75, 2.63). A similar pattern of increased risk was found for history of sexually transmitted disease. Use of iron supplements was indicative of decreased ALL risk (OR = 0.67, 95% CI: 0.47, 0.94). Observing an increased risk of leukemia in children of mothers reporting a history of influenza/pneumonia and sexually transmitted disease around the time of pregnancy suggests that maternal infection might contribute to the etiology of leukemia. Furthermore, maternal iron supplement use may be protective against childhood leukemia.