In small preliminary trials, ciprofloxacin has failed to eradicate Helicobacter pylori. Since fluoroquinolones have a marked reduction in bactericidal activity at acidic pH, we altered the gastric pH using omeprazole and investigated the efficacy of ciprofloxacin in eradicating H pylori. Forty-four consecutive patients infected with H pylori were prospectively studied in a randomized, double-blind, controlled trial comparing ciprofloxacin with a placebo for 2 weeks. Both treatment groups received bismuth and omeprazole. In 36 patients, follow-up endoscopy was done 4 weeks after the cessation of all study drugs. The H pylori infection cleared in 13 of 17 patients (76%) in the ciprofloxacin group versus 5 of 19 (26%) in the placebo group. Concurrent administration of omeprazole with ciprofloxacin resulted in increased bactericidal activity against H pylori. Ciprofloxacin when combined with omeprazole and bismuth is efficacious for eradication of H pylori.