Cellular resistance to cisplatin can develop during irradiation and antineoplastic therapy. Due to several mechanisms described, a multifactorial genesis is discussed. Clinical studies in testicular cancer reached complete response cure up to 95% by using a cisplatin-containing regimens. In case of primary or secundary platinum-resistance the application of newer platinum agents (e.g. oxaliplatin) are currently under detection. The molecular pathways of cellular resistance to oxaliplatin have not been clearified yet, but there are several indications for similar mechanisms. In this study human testicular cancer cell lines 2102 EP and H 12.1 were compared after a fractionated irradiation on alterations in radiosensitivity, chemosensitivity and expression of several proteins related to apoptosis and DNA-repair. Basically both cell lines showed similar results: No significant change were induced in radiosensitivity, but some results approach that at low radiational level (1Gy) a sensibilization could be induced. Interestingly fractionated irradiation leads to higher sensitivity to cisplatin but reduced sensitivity to oxaliplatin. Protein analysis showed an upregulation of several stress response molecules, e.g. Parp, p53, p21, Bax, hMSH2 and Fas. Sensibilization to cisplatin seems to be a result of a lower apoptotic treshold, a mechanistical basic of synergistic action of cisplatin and irradiation. The induction of oxaliplatin resistance after irradiation, described for the first time in literature, has not been fully understood. If those results are going to be confirmed in further studies, use of oxaliplatin after ionizing irradiation may be considered critically.