A strain of Leptospira zanoni was used to produce chronic renal infections in young white mice. A variant of this strain produced an acute disease with over 50% mortality. The responses of both forms of disease to chemotherapy were studied. When treatment of the acute disease was initiated before jaundice occurred, suitable single doses of streptomycin, chlortetracycline, tetracycline, erythromycin, oxytetracycline and oxytetracycline (in oil) prevented death and chronic renal infection in a high percentage of mice. Bicillin, a long-acting penicillin preparation, was more effective than other penicillins, but it prevented the development of chronic renal infection in only half the treated mice. Streptomycin was the only antibiotic of which a single administration regularly cured the chronic renal infections: chlortetracycline, tetracycline and oxytetracycline (in oil) were partially effective. Oxytetracycline, chloramphenicol, Bicillin, fortified penicillin, procaine penicillin and potassium penicillin had no permanent action. The suitability of mice as laboratory animals in the study of experimental leptospirosis and the need for complete cure of carriers of chronic renal infection are emphasized. The above findings indicate that streptomycin is the drug of choice for the treatment of leptospirosis in animals, and that it is worthy of further trial in man.