High relapse rates and low tolerability to ampicillin characterize present therapy for carriers of Salmonella typhi. Norfloxacin, a carboxyquinolone with a 90% minimum inhibitory concentration for S. typhi of ≤0.5 µ/mL, is a promising alternative. Carriers of S. typhi were treated in a double-blind trial with either norfloxacin (400 mg) or matching placebo given every 12 h for 28 d. Twelve assessable individuals were treated in each group. After therapy, 11 of 12 individuals treated with norfloxacin had negative stool and bile cultures for S. typhi. All placebo-treated carriers still had positive cultures immediately after therapy. Subsequently, 11 individuals were treated openly with norfloxacin. S. typhi was eradicated in seven of 11. Overall, the eradication rate for 23 individuals treated with norfloxacin was 78%. Eighteen individuals were followed up for one year, and their stool and/or bile cultures remained negative. From our results, norfloxacin is an effective and well-tolerated antimicrobial agent for eradicating the chronic typhoid carrier state. © 1988 by The University of Chicago.