Clinical and epidemiological studies suggest that genetic factors may be involved in the etiology and pathogenesis of testicular germ-cell tumors (GCTs). Previous HLA studies have tried to support the concept of genetic anticipation of GCTs, however, the results obtained have been inconsistent. The reasons for the divergent results are mainly statistical problems, i.e., small patient populations, high numbers of antigens tested, and inhomogeneous study populations. In the present retrospective study, 52 patients with histologically pure seminoma were typed for their HLA-A, B, C, and DR antigens. Only BW41 proved to be significantly increased in frequency after correction for the number of antigens tested (chi Q = 12.73; P = 0.0005). HLA-DR1 was shown to be decreased, however, the difference was not significant. Regarding metastatic seminoma alone, there was a trend towards an increase of A29, BW41, and DR7. Our study gives only weak evidence for the participation of genetic factors in the pathogenesis of seminoma. The statistical trend of HLA association observed in metastatic seminoma deserves further concern as does the question of whether MHC class II antigens are also involved in the pathogenesis of testicular seminoma.