Peripheral blood monocytes from polar lepromatous leprosy (LL) patients were unable to support Mycobacterium leprae-induced in vitro lymphoproliferation of HLA-D-matched T cells from tuberculoid leprosy subjects, whereas those from responder individuals were able to do so. Monocyte-rich adherent cells from untreated LL patients released de novo soluble factors which inhibited antigen-induced lymphoproliferation to a greater extent and mitogenic responses to a lesser extent. Suppressive activity varied in different LL patients. However, the degree of suppression was similar in soluble factors obtained de novo and after treatment of adherent cells with heat-killed and freshly extracted, cryopreserved M. leprae. Treated patients showed less inhibition with de novo released soluble factors (27 +/- 7.7%) as compared to parallel soluble factors obtained after antigen treatment (44 +/- 4.8%) or with de novo soluble factors from untreated LL patients (62 +/- 14.2%). Similar supernatants from tuberculoid individuals showed no or insignificant effects on antigen-induced lymphoproliferation. The suppressive activity of LL soluble factors was produced for up to 72 h, was heat stable at 56 degrees C for 30 min, was indomethacin resistant, and resided in the greater than 25,000 molecular weight fraction.