We conducted a randomized, double-blind clinical trial to compare ciprofloxacin (250 mg oncea day for 3 days) with tetracycline (500 mg four times a day for 3 days) in terms of efficacy and safety in the treatment of moderate-to-severe cholera in Peruvian adults. The baseline characteristics of the groups were similar. A total of 202 patients (102 in the tetracycline group and 100 in the ciprofloxacin group) were included in the efficacy analysis. The clinical and bacteriologic efficacies ofthe two regimens were similar. The study drugs were well tolerated. We conclude that ciprofloxacin given once a day is as effective as the standard tetracycline regimen for the treatment of cholera in adults. The ciprofloxacin regimen may represent an alternative to the standard treatment in areas where Vibrio cholerae O1 strains that are resistant to commonly used antimicrobials are prevalent. © 1995 by The University of Chicago. All rights reserved.