We examined the antitumor effects of human recombinant tumor necrosis factor alpha (rhTNF-alpha) and its muteins with the N-terminal amino acid sequence altered by point mutations against transplantable Morris hepatoma 5123 in rats. In vivo studies showed antiproliferative activity of the drugs in the dose range tested. For in vivo studies rhTNF-alpha and muteins were administered intratumorly (i.t.). The preparations were given at a dose of 10 microg/rat, once daily for eight days. Although the therapy was significantly effective in inhibiting tumor growth, complete growth inhibition could not be achieved. Nevertheless, there was a significant increase in survival time of tumor-bearing rats.