Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0-15%. Clarithromycin has potential advantages over other macrolides to which H. pylori is susceptible because of its acid stability and solubility at low pH. We evaluated clarithromycin therapy (250 mg four times daily for 14 days) in 12 H. pylori-infected patients. The 13C-urea breath test was used to evaluate the effectiveness of therapy. Eradication was defined as a negative urea breath test 4-6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 11 of 12 patients (92%) by a negative urea breath test 2 days after start of treatment. H. pylori was eradicated in five (42%) of 12 patients. Adverse events were intermittent and mild. Clarithromycin is the first antimicrobial agent that appears to offer promise as monotherapy for the eradication of H. pylori.