To determine the usefulness of detailed histopathological evaluation in the assessment of urovirulence of different Escherichia coli strains in a mouse model of ascending, unobstructed urinary tract infection, and to evaluate the relationship between susceptibility to urinary tract infection and renal levels of P fimbrial receptor glycolipids in different mouse strains, female Swiss Webster and Balb/c mice were inoculated transurethrally with one of four different well-characterized wild type E. coli strains or with an E. coli K-12 laboratory strain, and renal glycolipid levels were determined for both mouse strains. In Swiss Webster mice, each of the wild type E. coli strains was more virulent than the laboratory strain by both microbiological and histopathological criteria. Despite the common origin and identical virulence factor profiles of the three urosepsis isolates studied, one was significantly less urovirulent than the other two. Paradoxically, this strain stimulated a greater degree of leukocytosis than did the more urovirulent strains. Balb/c mice were significantly more susceptible to infection with this strain than were Swiss Webster mice, a difference possibly contributed to by the significantly higher renal levels of P fimbrial receptor glycolipids in Balb/c mice. Detailed histopathological analysis revealed significant differences in virulence between bacterial strains, and in susceptibility to infection between different mouse strains, that were inapparent from culture results alone.