The relation between parents' tobacco smoking prior to birth and cancer in the offspring was investigated with the use of data from a case-control study. Incident cases included all children (aged 0-14 years) diagnosed in Denver, Colorado from 1976 to 1983. Controls were selected through random digit dialing, and matched to cases on age, sex, and geographic area. Information on smoking by parents and other household members was obtained by personal interview for 223 cases and 196 controls. After adjustment for father's education, mother's smoking during the first trimester of pregnancy was associated with an increased risk for all cancers combined (odds ratio (OR) = 1.3, 95% confidence interval (CI) 0.7-2.1), acute lymphocytic leukemia (OR = 1.9, 95% CI 0.9-4.1), and lymphomas (OR = 2.3, 95% CI 0.8-7.1). Adjusting for father's education, associations with father's smoking in the absence of mother's smoking were found for all cancers combined (OR = 1.2, 95% CI 0.8-2.1), acute lymphocytic leukemia (OR = 1.4, 95% CI 0.6-3.1), lymphomas (OR = 1.6, 95% 0.5-5.4), and brain cancer (OR = 1.6, 95% CI 0.7-3.5). In spite of imprecision resulting from small numbers of cases in diagnostic subgroups, these results are suggestive of a possible influence of parents' smoking on childhood cancer.