To compare the efficacy of ciprofloxacin, erythromycin, nalidixic acid and pivmecillinam in the treatment of tetracycline-resistant strains of Vibrio cholerae O1 in adults, a randomized, open, clinical trial was conducted. A tetracycline group was used for comparison. Seventy-five adult men infected with V. cholerae O1 were randomly assigned to receive either 400 mg pivmecillinam or 500 mg of one of each of the other drugs. Ciprofloxacin was given every 12 h and the others every 6 h for 3 d. The mean total stool volume per kg was 155 mL for the ciprofloxacin group, 212 mL for the erythromycin and pivmecillinam groups, 246 mL for nalidixic acid, and 293 mL for tetracycline. The difference between ciprofloxacin and tetracycline was significant (P = 0.045). After 72 h, diarrhoea had stopped in 14 patients (93%) in the ciprofloxacin group and 12 (80%) in the erythromycin group, compared to 5 (42%) of those receiving tetracycline (P = 0.006 and 0.049, respectively). Bacteriological clearance was 100% at 24 h in patients treated with ciprofloxacin compared to 20% and 8.3% (P < 0.001 for both comparisons) in the erythromycin and tetracycline groups. Ciprofloxacin in conjunction with appropriate fluid therapy was the most effective treatment for cholera in adults; erythromycin was the next best.