The authors examined the relation between birth weight, intrauterine growth, and risk of childhood leukemia using population-based linked health data from Western Australia. A cohort of 576,593 infants born in 1980-2004 were followed from birth to diagnosis of acute lymphoblastic leukemia (ALL) (n = 243) or acute myeloid leukemia (AML) (n = 36) before their 15th birthday, death, or the end of follow-up (December 31, 2005). Data were analyzed using Cox regression. Risk of ALL was positively associated with the proportion of optimal birth weight-a measure of the appropriateness of fetal growth-particularly among children younger than 5 years; the hazard ratio for a 1 standard-deviation increase in proportion of optimal birth weight was 1.25 (95% confidence interval: 1.07, 1.47). Among children younger than 5 years not classified as having high birth weight (defined as > 3,500 g, > 3,800 g, and > 4,000 g), a 1-unit increase in proportion of optimal birth weight was associated with an approximately 40% increase in ALL risk. This suggests that accelerated growth, rather than high birth weight per se, is involved in the etiology of ALL. These findings are consistent with a role for insulin-like growth factor I in the causal pathway. Findings for AML were inconclusive, probably because of small numbers.