A series of drugs that had been found active against Mycobacterium leprae in mice by the continuous method of drug administration was tested by the kinetic method. Vadrine and viomycin were found inactive. Cephaloridine, streptovaricin, and rifampin gave bactericidal-type results. In a second experiment, rifampin was found to have distinct bactericidal effect when given for only 2 days. The plasma levels of rifampin that were associated with bactericidal effect in mice were in the range reported for man receiving acceptable dosages of rifampin. Cephaloridine and, especially, rifampin merit further investigation in clinical trials in leprosy patients, either as single drugs or in combination with other active drugs. The combination of rifampin and dapsone (DDS) or acedapsone (DADDS) appear to provide the advantages of both drugs.