Evidence has emerged that childhood leukemia is initiated in utero. High birth weight is one of the few birth-related factors that has been associated with childhood leukemia, albeit not consistently. The authors conducted a meta-analysis of studies of the association between birth weight and childhood leukemia risk. Study-specific odds ratios for leukemia were calculated, using a cutoff at 4,000 g of birth weight. The authors also evaluated whether the association between birth weight and leukemia followed a log-linear dose-response-like pattern. They calculated summary estimates using weighted averages of study-specific odds ratios from dichotomous and trend analyses. Eighteen studies (published between 1962 and 2002) were included, encompassing 10,282 children with leukemia. Children weighing 4,000 g or more at birth were at higher risk of acute lymphoblastic leukemia than children weighing less (odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.17, 1.37). Furthermore, data were consistent with a dose-response-like effect (OR = 1.14/1,000-g birth weight increase, 95% CI: 1.08, 1.20). Studies of acute myeloid leukemia indicated a similar increase in risk for children weighing 4,000 g or more at birth (OR = 1.27, 95% CI: 0.73, 2.20) and a dose-response-like effect (OR = 1.29/1,000 g, 95% CI: 0.80, 2.06), but results varied across studies. Our findings support a relation between birth weight and childhood acute lymphoblastic leukemia risk and emphasize the need for additional studies of the biologic mechanisms underlying this association.