Clinical observations, epidemiologic data, and results of animal experiments support the theory of genetic anticipation of testicular germ-cell tumors. Attempts to find genetic markers of testicular cancer have yielded conflicting results. We studied blood groups of 577 patients treated for testicular germ-cell tumor (GCT) and controls. Lewis antigens of 143 patients treated for testicular GCT, and controls, and HLA antigens of 215 patients treated for testicular GCT and controls. Blood-group frequencies were the same in patients and controls. Lewis antigen Le(a-b-) was more frequent in patients than in controls (p = 0.046; RR = 2.38). HLA Bw41 was associated with seminoma (p = 0.0001; RR = 8.2). None of the previously reported associations of other HLA antigens with GCT was confirmed. We found no association of HLA antigens with susceptibility to metastatic disease. The associations of Le(a-b-) with testicular GCT and of HLA Bw41 with seminoma support the contention that genetic factors are involved in the etiology and pathogenesis of GCT. HLA-Bw41 could possibly be employed as a risk marker for seminoma.