Certain cytokines, particularly gamma-interferon (IFN) and interleukin (IL)-2 associated with T(H)1 cell function, have been shown to play a role in allograft rejection. One paradigm for long-term allograft acceptance involves T(H)2 cytokine predominance (IL-4 and IL-10). We describe two renal allograft recipients for whom immunosuppression was discontinued due to serious sepsis and who maintained stable renal function over 2-6 months without immunosuppression. During this time, there were higher levels of both IFN-gamma and IL-10 in the peripheral blood than in stable control kidney transplant recipients on immunosuppression. In one of the patients, levels of IL-10 fell, while those of IFN-gamma remained persistently elevated. This was associated with biopsy-proven rejection. Although peripheral blood cytokine levels may not reflect intragraft events, these data are consistent with an allograft protective role for IL-10 offsetting that of IFN-gamma in both patients off immunosuppression.