The neonatally thymectomized Lewis rat (NTLR) is highly susceptible to infection with M. leprae. However, a significant percentage of NTLR respond to infection with M. leprae in much the same way as do intact rats, yet show no evidence of residual thymus. To determine whether there was a correlation between the number of remaining T-cells and susceptibility to infection with M. leprae, a direct fluorescent antibody test was performed using a highly specific, absorbed antithymocyte globulin labeled with fluorescein isothiocyanate. Both total circulating white blood cells and T-cells were significantly depressed in all NTLR examined. Although the greatest numbers of M. leprae were found in NTLR from the groups having the lowest percentage of circulating T-cells, these groups also contained NTLR infected with small numbers of M. leprae. The groups containing NTLR with the highest percentages of circulating T-cells also contained animals with both moderate and severe M. leprae infection. The response of cultured splenic lymphocytes from NTLR and normal rats to the T-cell mitogen concanavalin A was investigated to determine whether there was any correlation between T-cell activity and susceptibility to M. leprae infection. The mean stimulation index for normal rats was five to ten times greater than indices for NTLR, but there were no significant differences between NTLR with a well developed, generalized infection and those with a poorly developed infection. it was concluded that since there was no apparent relationship between T-cell depletion and susceptibility to infection with M. leprae, an additional, unknown mechanism was also involved.