Monocytes and macrophages are an important host defense in humans infected with Salmonella enterica serovar Typhi. Bacterial ability to survive in these cells is therefore a crucial virulence characteristic of this pathogen. In this study, we demonstrate that growth of a Salmonella enterica serovar Typhi enterochelin synthesis mutant and a tonB mutant in the human monocyte cell line Mono Mac 6 is restricted compared to that of the parental wild-type Ty2 strain. These results suggest that enterochelin-and TonB-mediated iron uptake plays a role in S. enterica serovar Typhi pathogenesis, and also suggest that mutations in iron uptake may attenuate S. enterica serovar Typhi strains for human beings. ß