Increased birth weight previously has been reported to be associated with childhood acute leukemia although the etiologic importance of this finding remains unclear. To further assess birth weight and associated parameters as a risk factor for childhood leukemia, a case/control study was performed using children with acute lymphoblastic leukemia (ALL) born in the state of Minnesota and diagnosed since 1969. Data obtained from birth registrations of 219 cases were compared with two control groups matched on date and county of birth (group I) or year of birth (group II). No significant differences were observed in mean birth weights of cases and controls. Statistically significant associations with birth weights greater than 3800 g were identified in cases diagnosed within the first 4 years of life. No associations were found between birth weight and ALL for case children diagnosed after 4 years of age. Factors that might be associated with increased birth weight, including maternal age, birth order, length of gestation, and socioeconomic status as measured by paternal education, were not found to be associated with an increased risk for ALL. The significance of the finding of high birth weight as a risk factor for childhood ALL remains unknown but suggests that pregnancy-related events may be of importance in the etiology of ALL in young children.