Sahnonella typhi (S. typhi) is an important pathogen which causes typhoid fever. The cytokines released from the macrophages, playing a role in the host defense against Sahnonella infection, are crucial in the defense against the infection. IFN-gamma provides a protection against Salmonella infection by developing macrophage activation in different mechanisms. This study was designed to investigate the effect of the recombinant IFN-gamma (rIFN-gamma) on the cytokines secreted froth S. typhi stimulated macrophages. Macrophage isolation was done in the heparinized blood samples obtained froth healthy people, and following the priming with rIFN-gamma for 72h the cells were stimulated by S. typhi and then the cytokine levels in culture supernatants were determined by enzyme-linked immunosorbent assay. It was observed that rIFN-gamma reversely increased the levels of IL-1, IL-2 the levels of which were decreased by S. typhi and that it increased TNF-alpha levels while suppressing the levels of antiinflammatory cytokines such as IL-10 and TGF-beta the levels of which were increased by S. typhi. Consequently, rIFN was observed to increase protective Th1 response by affecting the secretion of cytokine during S. typhi infection and it was considered to be a good target especially to prevent and treat invasive Sahnonella infections. 2007 Elsevier Ltd. All rights reserved.