The relation between birth characteristics and leukemia in young children was investigated in a large population-based study in California. Cases were obtained from the statewide cancer registry for 1988-1997. During this time, 1,957 leukemia cases were diagnosed among children under age 5 years. Of these, 1,728 (88%) were matched to a California birth certificate. Two control birth certificates, matched on date of birth and sex, were randomly selected from the statewide birth registry for each case. Analyses were performed separately for acute lymphoid leukemia (ALL) and acute nonlymphoid leukemia (ANLL). Odds ratios and 95% confidence intervals were estimated from conditional logistic regression. The strongest finding was for greatly increased risk of both types of leukemia in children with Down's syndrome (22 cases and no controls). African-American children had strikingly decreased risk for ALL (odds ratio (OR) = 0.29, 95% confidence interval (CI): 0.20, 0.42), and Asian/Pacific Islanders had increased risk for ANLL (OR = 2.00, 95% CI: 1.19, 3.36). Older maternal age was associated with slightly increased risk for ALL (maternal age > or =35 years, OR = 1.25, 95% CI: 1.04, 1.52), although this odds ratio was somewhat reduced when adjusted for other factors. No strong relations were observed for birth weight and ALL or ANLL.