Human rIL-1 alpha and human rIL-1 beta were examined for their ability to potentiate the lethal and hypothermic effects of mouse rTNF-alpha in mice. The LD50 of rTNF-alpha was 1.5 micrograms/mouse, whereas the LD50 of rTNF-alpha was reduced to 0.4 micrograms/mouse and 0.5 micrograms/mouse when rTNF-alpha was administered in combination with a nonlethal dose of rIL-1 alpha or rIL-1 beta, respectively. A similar rTNF-alpha enhancing effect of the rIL-1 was observed on the temperature response. The results show that the rIL-1 markedly potentiate the effects of rTNF-alpha on lethality and temperature in mice, and support our suggestion that TNF-alpha and IL-1 may have synergistic lethal effect in human septic shock.