With the aim to increase anti-tumor effectiveness of electrochemotherapy, adjuvant immunotherapy with tumor necrosis factor-alpha (TNF-alpha) was tested on tumors in mice. Increased anti-tumor effectiveness on SA-1 tumors was observed after combining TNF-alpha, injected either intratumorally or peritumorally, with electrochemotherapy using suboptimal dose of bleomycin (BLM). The increased anti-tumor effectiveness was neither the result of potentiated anti-tumor effectiveness of TNF-alpha due to exposure of tumors to electric pulses, nor due to interaction with BLM. Therefore, the effect of adjuvant TNF-alpha treatment might be immunomodulatory, augmenting the anti-tumor activity of electrochemotherapy, and possibly adding a systemic component to the localized electrochemotherapy treatment.