This investigation was carried out to study the possibility of eliciting favourable immunological changes in small groups of Mitsuda-negative patients with indeterminate leprosy, lepromatous patients who were bacteriologically negative after prolonged treatment with sulphones, and in Mitsuda-negative contacts by means of stimulation with a mixture of autoclaved tissues from Mycobacterium leprae-infected armadillos and living BCG. A radical change was observed in the specific immunological activity of the indeterminate group, all of whom initially had occasional bacilli in cutaneous nerves in biopsies taken from hypopigmented spots, and in the persistently Mitsuda-negative contacts. The 48 hr and 30 day reactions to lepromin, the 48 hr reaction to supernatant antigen from lepromin, the test for bacillary clearence and in vitro lymphocyte transformation (LTT) to M. leprae from human and armadillo lesions all became positive. Of the lepromatous patients studied, only one became positive to all the criteria mentioned above. In the others, the 48 hr reaction to supernatant antigen, the LTT to antigen from a humn source, and the clearance test remained negative, while the Fernandez and Mitsuda reactions became positive. These results are discussed in terms of the possible use of this stimulation procedure in the prevention and immunotherapy of leprosy.