Exposures to carcinogenic compounds from vehicle exhaust may increase childhood leukemia risk, and the timing of this exposure may be important. We examined the association between traffic density and childhood leukemia risk for three time periods: birth, time of diagnosis, and lifetime average, based on complete residential history in a case-control study. Cases were rapidly ascertained from participating hospitals in northern and central California between 1995 and 2002. Controls were selected from birth records, individually matched on age, sex, race, and Hispanic ethnicity. Traffic density was calculated by estimating total vehicle miles traveled per square mile within a 500-foot (152 meter) radius area around each address. We used conditional logistic regression analyses to account for matching factors and to adjust for household income. We included 310 cases of acute lymphocytic leukemias (ALL) and 396 controls in our analysis. The odds ratio for ALL and residential traffic density above the 75th percentile, compared with subjects with zero traffic density, was 1.17 [95% confidence interval (95% CI), 0.76-1.81] for residence at diagnosis and 1.11 (95% CI, 0.70-1.78) for the residence at birth. For average lifetime traffic density, the odds ratio was 1.24 (95% CI, 0.74-2.08) for the highest exposure category. Living in areas of high traffic density during any of the exposure time periods was not associated with increased risk of childhood ALL in this study.