After injection of 10(8) live Mycobacterium lepraemurium (MLM) into the left hind footpad of mice, there is development of local swelling attributable to a granuloma of the cell-mediated immunity type. Concomitant intravenous inoculation of live MLM delays and may even suppress footpad swelling, the effects being proportional to the intravenous dose of organisms. Concomitant footpad infection and intravenous inoculation of 10(9) dead MLM also delays footpad swelling, but over a period of months the feet become excessively swollen. The excessive swelling is due to local enhancement of infection as evidenced by an increase in the number of MLM per footpad. Attempts were made to prevent such immunosuppression by splenectomy or treatment with BCG. Splenectomy was entirely without effect, but 10(7) live BCG administered intravenously 2 to 4 weeks before dead MLM prevented enhancement of infection. The mediator of the immunosuppressive mechanism that results in enhanced infection remains to be elucidated, but it is unlikely to be antibody or immune complexes.