An occupation-and-exposure linkage system was utilized to perform an epidemiologic case-control study of paternal occupation and Wilms' tumor in offspring. The first part of the study was designed to test the hypothesis that paternal lead (Pb) exposure is a risk factor for Wilms' tumor in offspring. The second part of the study was an exploratory analysis that sought to generate possible etiologic hypotheses about other paternal exposures in the workplace in relation to Wilms' tumor. Calculation of odds ratios indicated that there was no statistical difference in the frequency of occupational exposure to Pb, Pb alkyls, and Pb salts for fathers of children with Wilms' tumor and fathers of controls, a finding that contrasts sharply with the results of the one previously reported study in this area. In the exploratory phase of the study, case fathers were found more likely to have been exposed to boron, while control fathers were found more likely to have encountered insecticides, acetylene, o-chlorobenzylidene, oil orange ss, and diethylene glycol; the differences were statistically significant. Troublesome methodologic problems, including exposure misclassification, sample size, and multiple comparisons, are discussed.