Surveillance of Helicobacter pylori antibiotic susceptibility from patients in London, the largest metropolitan area in the UK, is limited, despite resistance being a key factor in treatment failure. A two-centre survey was performed over 12 months (1999-2000) to determine antibiotic-resistance rates of isolates from dyspeptic patients attending endoscopy clinics serving two ethnically diverse central and south London communities. The in vitro antibiotic susceptibilities were determined from disc diffusion and epsilometer (E) tests on 101 H. pylori isolates. Overall resistance rates were 59% for metronidazole and 11% for clarithromycin, with 8% resistance to both antibiotics. Corresponding primary resistance rates were 50% and 7%, respectively. High-level-resistance was a feature of 82% of the metronidazole (MIC ≥ 256 mg l-1) -resistant and 55% of the clarithromycin (MIC ≥ 32 mg l -1) -resistant strains. All isolates were susceptible to amoxycillin and tetracycline. No associations between resistance and either the gender or the age of the patients were detected. The main risk for resistance to metronidazole was non-UK birth as comparative rates were 68% for non-UK vs. 40% for UK-born individuals. Resistant isolates were genotypically diverse with respect to cagAlvacA type. Four 23S rDN A nucleotide polymorphisms were associated with clarithromycin resistance, mostly (9/11) at A2143G. In conclusion, the high overall metronidazole-resistance rate of 59% for H. pylori from inner London was twice the rate found in other UK-based studies and was attributed to the higher risk of resistant strains infecting individuals born outside the UK. The need for continued resistance surveillance is indicated to monitor the effects of the 'test and treat' strategy for H. pylori eradication, particularly of isolates from at-risk individuals.