In our recent study of childhood rhabdomyosarcoma (RMS) we found an increase in the risk of RMS among children whose fathers smoked cigarettes. However, there was no association between RMS and mothers' smoking. We hypothesize that differential germ cell damage from cigarette smoking underlies our observations and that this risk of germ cell damage from cigarette smoking and from other environmental exposures is greater for men than for women. The increased susceptibility for male germ cells may be due to the number and timing of meiotic and mitotic cell divisions. In males, germ cells undergo large numbers of meiotic and mitotic divisions throughout the reproductive years. In contrast, in females, generally only one oocyte matures and completes meiosis each month of the reproductive years. Thus, there are very large male-female differences in the number of rapidly dividing germ cells during the reproductive years, and it is rapidly proliferating cells which are most susceptible to genetic damage. We conclude that fathers' environmental exposures before conception of their children may play a role in the etiology of childhood cancer.