Epidemiologic methods only seldom identify causes of childhood cancer associated with relative risks below a factor of 1 1/2-2. Children are at risk of exposure to over 15,000 high-production-volume chemicals and are certainly exposed to many carcinogens. The individual impacts of most of these agents are too small to be detected, but collectively these unrecognized factors are potentially important. Infants and children are exposed to higher levels of some environmental toxicants and may also be more sensitive. During intrauterine development and childhood, cells divide frequently, and the mutant frequency rises rapidly. Endocrine-related cancers or susceptibility to cancer may result from developmental exposures rather than from exposures existing at or near the time of diagnosis. That environmental exposures may be important causes of childhood cancers is indicated by associations of enzyme polymorphisms with risk.