Escherichia coil grown in dipyridyl-induced iron-depleted conditions showed an appreciable reduction in relative cell surface hydrophobicity. Changes in the hydrophobicity markedly lowered the attachment of these bacteria to human uroepithelial cells in vitro. The role of cell surface changes induced by iron depletion, which may be induced in vivo, can have a bearing at the initial stages of infection. To comprehend the effect of these altered surface properties in urinary tract infection, a mouse model of ascending pyelonephritis was employed. Five out of the seven strains tested, when grown in iron-depleted medium, showed decreased renal colonization at 4 h post-infection. On the fifth post-infection day, this effect was absent, indicating that ultimate renal infection is dependent on other factors as well.