In December 1979, a Vibrio cholerae O1 resistant to tetracycline, ampicillin, kanamycin, streptomycin, and trimethoprim-sulfamethoxazole was obtained from a patient with cholera at the Matlab Hospital, Bangladesh. All 256 isolates of V. cholerae O1 stocked in the previous six months were tested for antibiotic sensitivity: 54 were resistant to tetracycline, and 44 of these were resistant to all five antibiotics. The clinical presentation and hospital course for 51 patients with resistant strains of V. cholerae O1 and 102 patients with sensitive strains were compared by their medical records. Patients with resistant strains were indistinguishable from controls by age, sex, or severity of symptoms at presentation. All were treated with tetracycline, and patients with the resistant strains purged longer (mean, 37 vs. 25 hr; P less than 0.01) and in greater volume (mean 4.3 vs. 2.3 liters; P less than 0.01) and their controls with cholera due to susceptible strains. A resistance plasmid was identified. Based on these results, antibiotic use in the areas with resistant vibrios must be reconsidered.