Summary Sixty skin biopsies taken from positive tuberculoid and borderline tuberculoid late lepromin reaction were studied using histological techniques. The distribution of mycobacterial antigen and nerves was demonstrated using immunochemical methods.A total of 557 nerve bundles was observed in 51 biopsies; 9 were devoid of nerves in the sections examined; 475 nerve bundles showed some relationship to the inflammatory infiltrate (85%); perineuritis being seen in 144 (30%) and endoneuritis in 5 (0'9%).Mycobacterial antigens inside the granuloma were detected in 59 of the 60 biopsies (98%). Only one specimen, showing a strong tuberculoid reaction, failed to show these antigens. On the contrary, mycobacterial antigen was absent in almost all nerves. Small deposits were detected in the perineurium of one nerve with perineuritis, and inside a Schwann cell of another, the latter belonging to a previously multi bacillary patient.The neurotropic tendency of the granuloma does not seem to be stimulated by the presence of mycobacterial antigens inside the nerves, as normally these antigens do not penetrate them. The hypothesis of some antigenic fraction of the neural tissue which cross-reacts with Mycobacterium /eprae antigens, thus eliciting a perineural or near-perineural inflammatory reaction is put fo rward, but needs fu rther investigation.During the last 70 years, the lepromin test has been widely used throughout the world to assess the immune status of leprosy patients and their contacts. The type of lepromin developed by Mitsuda in 1919, ' is still used today.The positive Mitsuda test, or late or delayed lepromin reaction, consists of a nodular induration of the skin, of varied size, at the site of the dermal inoculation of the 0305-7518/95/066277 +010 $1.00 © Lepra 277 278 L. Bakos and S. B. Lucas substance, reaching its maximum size between the third and fo urth weeks after the injection, slowly involuting afterwards, sometimes leaving an atrophic scar. Ulceration can occur in strongly positive reactions. Its presence is regarded as an indicator of resistance of the host to M. leprae infection, 2 -5 being the result of a delayed hyper sensitivity reaction to the injected antigen. 6 -8The inoculated antigens can be of human origin, obtained both by the Mitsuda or by the Dharmendra method from human lepromata, or of animal origin, obtained fr om armadillos experimentally infected with M. leprae.Histologically, the classical positive Mitsuda reaction consists of a dense grouping of epithelioid cells, with multinucleated giant cells and lymphocytes, thus forming a typical tuberculoid structure, similar to that encountered in TT or BT cases of leprosy. The size and type of cells in the granuloma can be variable according to the spectral concept of leprosy. 6 , 14 , 18The histopathology of the lepromin reaction has been extensively studied. 9 , 11 , 13 , l 6 Some authors note the preference for the inflammatory cells to be arranged around blood vessels and skin appendages, without referring specifically to nerves. 7...