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Electrochemotherapy is an antitumor treatment that utilizes locally delivered electric pulses to increase the effectiveness of chemotherapeutic drugs in cells and tissues. Electric pulses permeabilize tumor cells to allow non-permeant drugs such as bleomycin to enter the cells. Although preclinical data indicate that immune responsiveness of the organism is important for obtaining cures of the tumors after electrochemotherapy with bleomycin, it is not known how electrochemotherapy affects the immune system of the organism. The aim of the study was to determine the effects of electrochemotherapy with bleomycin on natural resistance and immune responsiveness. Natural resistance was evaluated by phagocytic and intra-cellular killing activity (oxidative burst) in monocytes and polymorphonuclear granulocytes from venous blood, and immune responsiveness by blast transformation of spleen mononuclear cells to mitogens. The percentage of monocytes in venous blood able to elicit oxidative burst was significantly increased 7 days after the electrochemotherapy and returned to normal values after 14 days. In addition, increased blast transformation of spleen mono-nuclear cells by stimulation with concanavalin A (T lymphocytes activity) was found 14 days after electrochemotherapy treatment. The results of our study demonstrate that electrochemotherapy with bleomycin affects the immune system of the organism.