Urinary tract infections (UTIs) are associated with approximately 27% of premature births. Escherichia coli is the most frequent causal agent of UTIs and expresses virulence factors, including surface adhesins that recognize specific host tissue receptors. We have reported that E. coli Dr adhesin recognizes decay-accelerating factor as the host tissue receptor and that these receptors are increased during pregnancy. Induction of pathogenesis is a cumulative effect of the host-pathogen relationship involving specific host factors and virulence characteristics of the invading organism. Recently, an experimental model of chronic pyelonephritis has been developed with E. coli bearing Dr adhesin (E. coli Dr(+)) in nonpregnant lipopolysaccharide hyporesponder C3H/HeJ mice. In this study, we investigated the role of E. coli Dr(+) on the outcome of pregnancy in C3H/HeJ mice. Groups of pregnant mice were infected with E. coli Dr(+) or its isogenic mutant which does not bear the Dr adhesin (E. coli Dr(-)) by urethral catheterization. Nearly 90% of pregnant mice infected with E. coli Dr(+) delivered preterm (before 90% gestation) compared to 10% of mice infected with E. coli Dr(-) and none of the mice treated with phosphate-buffered saline (PBS). Also, there was a significant reduction in fetal birth weight in the E. coli Dr(+)-infected group compared to the E. coli Dr(-)- and PBS-treated groups (P = 0.003). This experimental model of E. coli Dr(+)-induced preterm delivery in mice may help in understanding the molecular mechanisms involved in UTI-induced preterm labor involving bacterial adhesins.