The relF gene in Escherichia coli is related to the hok gene on plasmid R1. Both genes encode small proteins which, when overexpressed in E. coli lead to collapse of the membrane potential and cell death. A third gene, designated gef, which encodes a homologous cell-toxic protein, has been isolated from E. coli DNA. Both gef and relF are transcribed in E. coli and subject to post-transcriptional regulation which, in the case of gef, is coupled to translation of a leader sequence. The finding of homologous sequences in such distantly related bacteria as Agrobacterium and Rhizobium species suggests an important physiological role.