Time trends in incidence of disease may cast light on etiology. We investigated time trends in childhood leukemia by using Poisson regression methods to analyze data from the National Registry of Childhood Tumours, a long-standing high-quality registry that covers the whole childhood population of Britain. During 1974-2000, the average annual percentage change in rate (AAC) of childhood acute lymphoblastic leukemia (ALL) in Britain was 0.7% (95% confidence interval [CI] = 0.4 to 1.0). This increase was apparently driven by the "common" subtype (expressing the CD10 antigen) of precursor B-cell ALL, for which the estimated AAC during 1980-1996 was 1.4% (95% CI = 0.8 to 2.0). There was no statistically significant time trend in other subtypes of ALL combined (1980-1996) or in acute myeloid leukemia (1974-2000). Small peaks in incidence of ALL in 1976 and 1990 coincided with years immediately following influenza epidemics. These results are consistent with hypotheses that some childhood leukemia may be triggered by infection occurring close to the time of diagnosis of leukemia, particularly in conditions of low herd immunity, and raise the possibility that contact with influenza shortly before the diagnosis of leukemia may sometimes be involved.