Malignant transformation of germ cells is an early event in the development of testicular cancer, occurring in the fetal gonad of the mouse and possibly also in humans. Germ cells with the characteristics of CIS have been identified in human fetal testes, however, immunocytochemical markers for CIS in the adult are detectable in normal fetal and infantile testicular germ cells. It is possible that CIS cells are protected from immunosurveillance. There are differences between infantile and adult germ cell tumours (GCT) suggesting that their pathogenesis may be different. Seminoma cell lines are described although these are difficult to establish in cell culture. Chemotherapy may selectively destroy malignant GCT components leaving residual mature teratoma. It is unlikely that drug therapy induces differentiation. Second tumours without germ cell components may develop in GCT patients, but these second tumours are probably of germ cell origin. It is not clear if progression of untreated CIS to invasive tumour is inevitable. The possibility of spontaneous regression of CIS may also be considered.