Ulcerative colitis and Crohn's disease are more common among Jews than among non-Jews. Despite the existence of studies on the prevalence and incidence of inflammatory bowel disease in relation to the continent of residence or origin, there are no studies on the specific countries of origin of Ashkenazi Jewish patients. We report here the first analysis of 233 U.S. Jewish patients by defined world regions and subregions. Using two different sets of controls (a self-referred Jewish population for Tay-Sachs disease carrier detection and a sample of Jewish persons ascertained through unrelated studies from the same hospital as our patients), we found a significant excess of patients of middle European origin relative to those of Polish or Russian origin. These observations suggest that the inflammatory bowel disease gene(s) are more prevalent in the Jewish population that originated in middle Europe than in those from Poland and Russia. These results further suggest that Jewish patients with inflammatory bowel disease probably represent a nonrandom genetically predisposed subset of the Jewish population. This provides further evidence for the genetic contribution to inflammatory bowel disease in general, and to its higher risk in the Jewish population.