Two series of reinfection experiments were carried out using C57BL mice. In the first series, the mice were inoculated with Mycobacterium lepraemurium (MLM) in one hind footpad and reinoculated in the contralateral footpad, two or four weeks later. Compared with normal mice of the same strain, the mice reinoculated after four weeks showed an increased local reaction to the bacilli and the bacilli did not multiply at the injection site. The responses of mice reinoculated after two weeks were intermediate to those of the other two groups. In the second series, a systemic infection was established by intraperitoneal innoculation of either a large or small dose of MLM. Twenty-two weeks later the mice were reinoculated in one of the hind footpads. Upon reinoculation, mice receiving the small intraperitoneal dose reacted more strongly than normal mice to MLM, whereas mice receiving the large dose were unable to mount any local reaction to the mycobacterium. The experiments have shown that the local reaction which develops in the C57BL strain of mice approximately four weeks after subcutaneous injection of MLM is accompanied by the onset of systemic immunity. Such systemic immunity lasted for more than 20 weeks after intraperitoneal injection of a small dose of bacilli, but was completely abolished during the course of a heavy systemic MLM infection.