Helicobacter pylori infection causes chronic digestive diseases that disproportionately affect Hispanics and other immigrant groups in the United States. Information on the epidemiology of H. pylori infection in pregnant women who reside along the U.S.-Mexico border is critical to understanding the dynamics of current H. pylori transmission patterns within families along the border. We describe the epidemiology of H. pylori infection in pregnant women recruited from Women, Infants, and Children (WIC) clinics in El Paso, Texas, and Mexican Social Security Institute maternal-child clinics in Ciudad Juarez, Mexico, from April 1998 to October 2000. We interviewed participants regarding environmental factors and tested their serum for IgG antibodies. We used logistic regression to estimate associations between environmental exposures and the odds of H. pylori prevalence. Definitive serological tests were available from 751 women. Seroprevalence was 74% in Juarez women and 56% in El Paso women. Prevalence increased with age, crowding, poor sanitation, and residence in Mexico, decreased with education, and was not associated with the woman's number of living children. In the U.S.-Mexico border region, women of reproductive age have a high prevalence of H. pylori infection, apparently related to poor socioeconomic conditions.