Five patients with active leprosy, four with polar lepromatous (LL) and one with borderline lepromatous (BL) disease, were each treated with transfer factor (TF) from approximately 7.4 x 10(9) lymphocytes given in 36 divided doses over a 12-week period. The TF was prepared from blood donated by normal, healthy, lepromin skin test-positive individuals. During treatment all four of the LL patients, but not the BL patient, developed clinical reversal reactions. Histopathologically, skin biopsies in these four LL patients showed evidence of transformation of collections of multibacillary macrophages into paucibacillary epithelioid cells and giant cells. To our knowledge, this is the first histopahtologic documentation of reversal reactions occurring in polar LL. To the extent that reversal reactions are evidence of effective cell-mediated immunity of Mycobacterium leprae, these results indicate that TF is capable of at least partial correction of the immunologic deficit of lepromatous leprosy.