Yersinia pestis, the cause of bubonic plague, is transmitted by the bites of infected fleas. Biological transmission of plague depends on blockage of the foregut of the flea by a mass of plague bacilli. Blockage was found to be dependent on the hemin storage (hms) locus. Yersinia pestis hms mutants established long-term infection of the flea’s midgut but failed to colonize the proventriculus, the site in the foregut where blockage normally develops. Thus, the hms locus markedly alters the course of Y. pestis infection in its insect vector, leading ro a change in blood-feeding behavior and to efficient transmission of plague.