Severe combined immunodeficient (SCID), T cell deficient, and immunocompetent mice were challenged intravesically with viable uropathogenic Escherichia coli. In comparison to immunocompetent controls, SCID mice had significantly greater numbers of viable E. coli in their bladders and kidneys 7 days after inoculation. Splenic anti-E. coli antibody-forming cells (AFC) were virtually absent in SCID mice at 7.0 days after infection. Adoptive transfer of spleen cells from E. coli-immunized immunocompetent mice to SCID mice enhanced their resistance to urinary tract infection (UTI), as evidenced by lower bacterial counts in bladder and kidneys following an induced infection. Congenitally T cell deficient nude mice and immunocompetent heterozygous controls had equivalent bladder and kidney infection levels at 2 and 7 days after UTI. Immunocompetency thus appears to play a significant role in resistance to E. coli UTI in this animal model. Since mice deficient only in T cells did not show increased UTI susceptibility, T cell-independent antibody responses may be an important immunologic defense mechanism.