Using a rat model, we have previously demonstrated that infection with Cryptococcus neoformans can trigger the production of a series of suppressor cells that specifically inhibit the cell-mediated immune response to a non-related antigen, human serum albumin (HSA), that has been injected 7 days after the infection. We previously determined that the cryptococcal infection induces afferent suppressor or suppressor induction cells (Ts1) to HSA. The primary objective of the present study was to investigate the suppressor cells involved in the efferent phase of delayed-type hypersensitivity (DTH) response to HSA in rats infected with C. neoformans and immunized with the non-related antigen and determine the role that the Ts1 cell plays in the induction of that cell. For this purpose, the spleen mononuclear (SpM) cells containing the Ts1 or SpM cells from immunized non-infected rats (used as donor controls) were transferred to two groups of syngeneic naive recipients (first recipients). Later, the SpM cells from both groups of animals were transferred to rats immunized with HSA (second recipients). The efferent limb of the DTH response to HSA was suppressed in the recipients that received SpM cells from donors injected with Ts1 cells. Additional HSA antigen was not required for induction of these efferent suppressor cells. Furthermore, we here show that these cells are resistant to treatment with cyclophosphamide (Cy), and that they can activate another suppressor population. The latter are Cy sensitive and are present in the immune recipient.