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Frequent infections in early childhood, whole-day care and a socially unprivileged environment have been reported as protective factors for childhood leukemias and lymphomas. Conversely, a protected social environment, higher level of education and growing up in families with a low number of children are considered as risk factors. Additional risk factors involve agricultural occupation of the parents and exposure to several other occupational factors. These data led to a number of hypotheses that attempted to explain the epidemiologic observations; however, a number of questions are still open. Here we propose a new concept that could explain most of the epidemiologic characteristics. This concept is based on the assumption that persistent infections with TT virus-like agents increase the risk for specific chromosomal translocations. This risk should correlate with the viral load. Interferon induction by intermittent infections should reduce the viral load and thus decrease the risk for chromosomal modifications. Some virologic observations in support of this model are presented. © 2005 Wiley-Liss, Inc.