Mice inoculated with 4800 Mycobacterium leprae in the left hind foot pad were treated from day 62 to day 150 after infection with 50 mg or 150 mg of ofloxacin per kg body weight, 150 mg pefloxacin per kg, or 50 mg prothionamide per kg. These drugs were administered by esophageal cannula 5 days weekly with dapsone (0.01 g per 100 g diet). Multiplication of M. leprae in the treated and in untreated control mice was assessed by monthly harvests. The treatment of mice with the smaller dosage ofloxacin, with pefloxacin, prothionamide, or dapsone uniformly resulted in a delay of multiplication of 4 months, compared to the multiplication of M. leprae in the untreated controls. The delay of multiplication (4 months) being 1 month longer than the duration of drug administration (3 months), all of the treatments may be considered as bacteriopausal or moderately bactericidal. In contast with these results, treatment of mice with 150 mg ofloxacin per kg resulted in no growth of the organisms whatever as late as 18 months after inoculation, strongly suggesting that, in that dosage, ofloxacin had killed all of the M. leprae. Such a profound killing activity has been observed only with rifampin. Although the pharmacokinetic characteristics of ofloxacin are different in man from those in the mouse, the daily dosage of 150 mg ofloxacin per kg body weight in the mouse is equivalent to 400 mg per day in man which is the usual therapeutic dosage; thus, the results obtained in the mouse may be extrapolated to man. Therefore, ofloxacin appears a very promising drug for the chemotherapy of leprosy.