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Electropermeabilization (EPN), also termed electroporation, is a physical method to overcome the barrier of the cell membrane by applying short and intense electric pulses. It is the basis for a new cancer treatment modality, electrochemotherapy, where uptake of chemotherapeutics is enhanced by EPN. Preclinical and clinical trials have shown that application of electric pulses in vivo is feasible and that electrochemotherapy is highly efficient. The aim of this study was to develop an improved method of screening drugs on electropermeabilized versus non-electropermeabilized cells. In this study we describe an easy protocol which gives high cell viability, good reproducibility and a high rate of cell permeabilization. Cell cytotoxicity is simply determined by the MTT assay. Cell death due to the EPN procedure was less than 4% and more than 90% of cells were permeabilized. For daunorubicin, doxorubicin, etoposide and paclitaxel, no effect of EPN was found. For carboplatin and cisplatin the effect of EPN was a factor 3 and 2.3, respectively, on the IC50 (inhibitory concentration 50%). For bleomycin we found a dramatic effect of EPN of the magnitude of a factor 300 on the IC50. In conclusion, we have established a new, easy and reliable protocol to test new drugs for cytotoxicity with or without the limitations of the cell membrane. Our data support the role of bleomycin as the drug of choice for electrochemotherapy.