To determine the intracellular localization of intravenously injected infection-specific monoclonal antibodies (mAbs) in the infected cells, immunohistochemical staining was carried out in an animal model having pulmonary tuberculous lesions induced by inoculation of heat-killed Mycobacterium tuberculosis H37Rv. One milligram of intact mouse mAb against mycobacteria (group I, n = 10) and F(ab')2 (group II, n = 6) was intravenously injected to the rabbits of each group. Immunohistochemical staining using an antimouse Ab was performed at days 1, 3, 5, 7 and 8 in group I and at days 1, 2 and 3 in group II by the streptavidin-biotin method. For the control study, 1 ml of nonspecific polyclonal human IgG (group III, n = 10) and 100 micrograms of normal rabbit IgG F(ab')2 (group IV, n = 6) was injected to rabbits and guinea pigs having tuberculous inflammation, respectively. Both groups (group I and II) showed a positive antigen (Ag)-Ab reaction within the cytoplasm of monocytes. A weak but positive reaction was observed intracellularly in group III; however, no positive reaction was seen in group IV. Our results suggest that an intracellular Ag-Ab reaction plays an important role in the localization of infection by immunoscintigraphy using specific mAb fragments.