Anti-tumor effectiveness of tumor necrosis factor (TNF)-alpha applied peritumorally was assessed in combination with local electrotherapy on subcutaneous SA-1 tumors in mice. TNF and electrotherapy each induced significant tumor growth delay. In combined treatment using TNF and electrotherapy, a synergistic anti-tumor effect was observed, regardless of whether TNF was injected before or after electrotherapy. An extra anti-tumor effect was achieved when TNF in the same total dose (2 x 10(5) U) was split into a priming dose (0.5 x 10(5) U) 1 h before electrotherapy and the other (1.5 x 10(5) U) 24 h thereafter. As the result of this therapeutic combination survival rate of the animals was 40%. No animal survived more than 50 days in groups subjected to TNF or electrotherapy treatment alone. Combined treatment with TNF and electrotherapy induced massive tumor destruction, confirmed by histological examination 2 days after the treatment. The results indicate that TNF and electrotherapy interact and that they can be effective in control of local tumor growth.