The relationship between the level of delayed-type hypersensitivity (DTH) and the progression of Mycobacterium lepraemurium infection was examined after inoculation of mice with 10(8) M. lepraemurium in the left hind footpad. The expression of DTH developed over the first 4 weeks of infection, remained high up to week 8, and then dropped to a low level at which it remained for 12 more weeks. The development of DTH was concordant with an initial swelling of the inoculated foot, the appearance of a mononuclear infiltrate at this site, and a prevention of any increase in the number of mycobacteria in this foot and in other tissues studied. A decay of DTH reactivity was associated with a progressive increase in the number of M. lepraemurium initially at the original site of inoculation and subsequently in all other tissues. Although the expression of DTH was lost, adoptive immunization experiments showed that a population of sensitized lymphocytes persisted within host. Further experimentation offered evidence to suggest that the level of systemic antigen may be in part responsible for the loss of DTH reactivity.