PURPOSE: Specific events in the mother's reproductive history and certain birth characteristics have been associated with childhood leukemia. Few studies have explored these associations specifically in infants. METHODS: The Children's Cancer Group (CCG) conducted three separate case- control studies of childhood leukemia that involved similar methodologics and data collection. Data from interviews of the mothers of a total of 303 children diagnosed with leukemia at 1 year of age or younger a nd their matched controls (n = 468) were available from the three studies. These data included maternal reproductive history (stillbirths, abortions, and miscarriages) and certain birth characteristics of the index child. RESULTS: Compared with controls, cases were significantly more likely to be female (P < 0.01) and were more often heavier at birth (particularly cases diagnosed after 6 months of age (odds ratio, 4.18; 95% confidence interval, 1.75- 10.02)). Overall, there were no statistically significant differences between cases and controls in regard to maternal report of any type of previous fetal loss. Finally, being a later-born child was associated with an increased risk of acute myeloid leukemia but not of acute lymphoblastic leukemia. CONCLUSIONS: The relationships among birthweight, prior fetal loss, and risk of infant leukemia appear to be complex. Further studies of infant leukemia that incorporate molecular as well as epidemiologic data may help to elucidate these differences.