Normal human serum contains a heat-stable factor which is cytotoxic to Landschutz ascites tumor cells. The cytotoxic action requires the presence of human or rabbit complement but guinea pig complement is ineffective. The thermostable factor is found in the beta-globulin fraction and has characteristics similar to C4 of human complement. The absorption of this factor on mouse tumor cells takes place in the absence of Ca++ or Mg++; however, the cytotoxic effect on the cells is dependent on the presence of optimal concentrations of both Ca++ and Mg++. This factor is selectively absorbed on human and mouse tumor cells and human placenta but not by normal human liver, kidney or heart. HeLa and ascites cells treated with the stable factor became resistant to the action of heterologous antibodies.