Kings County Hospital (KCH), and St. John's Episcopal Hospital (SJH) are inner-city hospitals in New York City serving predominantly minority populations. Staten Island University Hospital (SIUH) serves a predominantly middle-class Caucasian population. We examined H. pylori (HP) infection in patients undergoing upper endoscopy at these hospitals. Two gastric biopsies were obtained from each patient. One biopsy was examined by histology or the rapid urease test for the presence of HP. The other was subjected to analysis by PCR to detect HP DNA and to identify putative HP virulence factors. Of 200 subjects, 54% were African-American, 10% were Hispanic, and 36% were Caucasian. HP infection rates in African-American, Hispanic, and Caucasian patients were 43%, 20%, and 11%, respectively. Many of the African-American patients are recent immigrants from the Caribbean Islands. In these patients, an inverse relationship was observed between HP infection and the number of years living in the United States. Higher levels of HP infection were observed in patients with duodenitis and peptic ulcer disease. With respect to HP virulence factors, the vacA s1b and m1 alleles, as well as the iceA2 allele were the predominant alleles expressed in HP-positive samples obtained from African-Americans. The cagA gene was detected in 81% of HP-positive samples. However, CagA positivity was not related to any specific gastrointestinal disorder. Our findings indicate that among several ethnic groups served by three hospitals, African-American patients have the highest rate of HP infection. Moreover, in AfricanAmerican patients undergoing endoscopy: (1) HP infection was inversely related to the number of years the patients have been living in the USA; (2) HP infection rates were higher in patients diagnosed with duodenitis and peptic ulcer disease versus other disorders; (3) expression of the CagA gene was not associated with any specific gastroduodenal disorder; and (4) there was little allelic heterogeneity with respect to VacA and IceA subtypes. These findings suggest that inner-city African-Americans are more likely to be infected with HP and suffer from more serious gastroduodenal disorders than other ethnic groups.