The administration of transfer factor obtained from three donors who had recovered from clinical infections with Mycobacterium xenopi to a patient who had a destructive pulmonary infection with this organism, was associated with the reversal of an unfavorable clinical course. Cavitary tuberculosis associated with resistance to all combinations of antituberculosis drugs was probably related to a concurrent depression of cell-mediated immunity of unknown origin. Antigen specific but not nonspecific transfer factor caused a rapid and prolonged improvement in both the pulmonary disease and the immunologic deficiency. Cross-reactivity between the antigenic determinants of M. xenopi and Mycobacterium tuberculosis made it possible to use transfer factor obtained from donors responsive to purified protein derivative of tuberculin. This study clearly demonstrates the additional benefits to be gained from using transfer factor that is antigen-specific in the treatment of infectious diseases.