Tumor necrosis factor (TNF) is a cytokine produced in vivo by activated macrophages and monocytes with pleiotropic effects on normal and malignant cells. TNF is cytotoxic to several tumor cell lines in vitro and in vivo. Phase I and phase II trials have been conducted to determine toxicity to humans and to evaluate responses. Recent investigations will be reviewed. Despite promising results in vitro and in vivo, data from systemic administration in the treatment of malignancies have been disappointing. Local administration has been successful. Therefore, we suggest that future efforts concerning TNF administration in the treatment of malignancies should aim at local treatment.