Delayed-type hypersensitivity was induced in cyclophosphamide-pretreated C3H/TifBom mice by subcutaneous immunization in the thorax with ultrasonicated Mycobacterium lepraemurium bacilli in Freund incomplete adjuvant. Seven weeks after immunization, 2.5 X 10(7) acid-fast M. lepraemurium bacilli suspended in diluted sonicate were injected into one hind footpad, and during the next 6 weeks three additional infections of sonicate were given at intervals into the infected footpad. After each injection a strong local reaction developed, which after the first three injections peaked at 24 h. The kinetics of the reaction was accelerated after the repeat injections. Each time the reaction subsided within 1 week. From 2 days to 11 weeks after the inoculation of bacilli there was a 10-fold increase in bacillary numbers in the footpad and a 3,000-fold increase in the draining popliteal lymph node. The degree of bacillary multiplication was the same in animals which had experienced repeated local reactions and in control animals. Thus, repeated strong delayed-type hypersensitivity reactions to M. lepraemurium antigens apparently were without any measurable effect on the bacillary multiplication. This observation provides further evidence for a dissociation in C3H/TifBom mice between delayed-type hypersensitivity to soluble mycobacterial antigens and protective immunity against mycobacteria. Possible explanations for our findings are discussed.