Mycobacterium marinum strains 1218 and 1219 were inoculated into the hind footpads of T-cell-depleted specific pathogen-free C57B1/6 mice, and the growth and survival of the organisms at the site of injection, the draining popliteal lymph node, and the spleen and lung were quantitated for up to 70 days. T-cell depletion largely ablated the normal cell-mediated antituberculous response to the M. marinum population. The mice were able to control the further growth of the inoculum within the footpad only after it had reached 5 to 10 times that present in the normal controls. The high temperature-adapted strain (37 C; strain no. 1218) induced an increasing infection in the liver, spleen, and lungs of the THXB mice, and the infection eventually spread to the opposite footpad and to the tail skin. Strain 1219 gave rise to considerable systemic involvement in the THXB host despite its inability to survive at 37 C, but the size of the splenic and lung populations was considerably lower than in the 1218-infected animals. Both M. marinum infections persisted in the tissues of the T-cell-depleted mice with no indication of a cell-mediated immune response. Footpad swelling in the M. marinum-infected mice was not greatly reduced by T-cell depletion, and, if anything, tended to persist at high levels long after the swelling of the control feet had gone into a decline. On the other hand, incorporation of tritiated thymidine by cells within the infected footpads, the draining lymph node, and the spleen was considerably reduced in the T-cell-depleted host compared with control values. Late in the infection, there was a significant increase in the amount of label taken up by the cells in the footpads of the T-cell-depleted host.