In 51 actively purging cholera patients the efficacy of doxycycline, a long-acting tetracycline, was compared with a placebo and tetracycline hydrochloride. Seventeen patients who were given doxycycline at the recommended dose of 2 mg/kg at the beginning of the study, at 12 h, and at the repeated dose once daily purged a mean volume of 5.1 liters of stool and received an average of 5.7 liters of intravenous fluid. Nineteen patients receiving the placebo purged 10.1 liters of stool and received 9.7 liters of fluid. Fifteen patients given tetracycline hydrochloride at 6-h intervals passed 4.8 liters of stool and received 5.5 liters of fluid. The durations of diarrhea calculated in 8-h periods were 3.5, 8.0, and 4.1 h in the respective groups receiving doxycycline, placebo, and tetracycline. The differences between the doxycycline and placebo treatments and the tetracycline and placebo treatments were statistically significant. Those receiving doxycycline became vibrio-free in about 3 days as compared with 2 days for those receiving tetracycline; the group given the placebo were vibrio positive for the duration of their hospitalization. The results show that in the treatment of cholera the administration of doxycycline once daily has effects equal to those when tetracycline is administered at 6-h intervals. This is a distinct advantage because it decreases the demand on nursing personnel in epidemics. Also, doxycycline may be safely administered in cases of suspected renal failure from prolonged shock in cholera.