One strategy for identifying genes involved in genetic predisposition to testicular germ-cell tumors (TC) is to perform association studies with polymorphic loci at or closely linked to candidate genes. Genes involved in normal fetal genital development, such as the Wilms' tumor 1 gene (WT1) located at 11p13, are among such candidates. The present study compares a TC (n = 442) and a control (n = 384) population for the allele frequencies of 2 polymorphic loci located at chromosome band 11p13. One of the polymorphisms (WT) was located within and the other (D11S325) in close proximity to the WT1 gene. No differences in allele frequencies between cancer patients and controls were found. However, the frequency of the Al allele of the WT polymorphism was significantly increased in one of the cancer subgroups most likely to carry susceptibility genes (patients with bilateral cancer) compared to controls. Furthermore, the frequency of the Al allele was increased in patients with metastatic disease. Such differences in allele frequencies were not observed for the D11S325 locus. The findings might indicate an involvement of the WT1 gene both in susceptibility to TC and in progression of the disease.