Twenty-four hour supernatants (MoF) were obtained from monocyte rich 2 h adherent cells of 19 leprosy patients and four healthy contacts. MoF from borderline and lepromatous patients produced 52-61% inhibition of human interleukin-2 (IL-2) production by a PHA conditioned T cell line (Jurkat). Non-adherent cell supernatants and MoF from tuberculoid and healthy individuals had little effect on IL-2 production. The suppression effected by MoF was in the first 12 h of initiation of PHA stimulated Jurkat cell cultures. Suppressive MoF did not interfere with (1) IL-2 release, (2) IL-2 utilization by Con A-induced T cell blasts or (3) constitutive proliferation of Jurkat cells. Such MoF were released spontaneously from adherent cells of bacilliferous leprosy patients but required in vitro antigen triggering in long term treated lepromatous patients. It is possible that the unresponsiveness associated with lepromatous leprosy is related to the inhibition of IL-2 production by suppressive factors, thereby, preventing the further expansion of antigen reactive T cells.