The failed attempt to express HIV-gp41 in E. coli led to the investigation of HIV-gp41 segments, which is responsible for the toxicity to E. coli cells. A series of dele-tion mutants containing different regions of gp41 gene were constructed and expressed in E. coli BL21(DE3) strain. After IPTG induction, the high mortality of host bacteria was ob-served in host bacteria carrying the deletion mutants of gp41 gene except for those transformed with pET-HN2; coordi-nately, the mRNA transcripts of the gp41 was rapidly de-creased; and the release of [3H]uridine increased upon in-duction. All these data suggested that GP41 protein has a cytotoxic effect on E. coli, and it is the cytotoxicity of the gp41 gene product that contributes to the high mortality when expressed in E. coli. The failed attempt to express HIV-gp41 in E. coli led to the investigation of HIV-gp41 segments, which is responsible for the toxicity to E. coli cells. A series of dele-tion mutants containing different regions of gp41 gene were constructed and expressed in E. coli BL21 (DE3) strain. After IPTG induction, the high mortality of host bacteria was ob-served in host bacteria carrying the deletion mutants of gp41 gene except for those transformed with pET-HN2; coordi-nately, the mRNA All these data suggest that GP41 protein has a cytotoxic effect on E. coli, and it is the cytotoxicity of the gp41 gene product that contributes to the high mortality when expressed in E. coli.