SUMMARYIn the immunosuppresscd burn patient serum levels of both IL-2 and a soluble form of IL-2 receptor alpha (sIL-2Rα) are significantly elevated. Strikingly, the production of these markers by the in vitro activated patients' cells is decreased. This study examines the role of IL-2 in the decreased production of the sIL-2Rαin vitro in patients with major burns (n = 18, 30 to > 70% total body suface area). Peripheral blood mononuclear cell (PBMC) cultures from patients with highly elevated serum sIL-2Rα. and from healthy controls (n = 12) were activated with concanavalin A (Con A) at initiation. In patients' cultures mitogen-induced increments of sIL-2Rα levels were significantly lower. There was a significant negative correlation (r= −0·64, P<0·001) between a high serum sIL-2Rα level and a decreased Iectin-induced sIL-2Rα release in vitro. Low levels of sIL-2Rα in patients' samples were not normalized by increasing the number of T lymphocytes. Also exogenous rIL-1 was without effect. whereas rIL-3 increased sIL-2Rα release in some cultures. However. sIL-2Rα levels were significantly increased in patients' cultures by (i) addition of exogenous IL-2; (ii) removal of adherent cells; (iii) addition of cyclooxygenase inhibitor, indomethacin: (iv) bypassing cell surface activation by the combination of the calcium ionophore A23187 and the phorbol ester 12-o-tetradreanoyl acetate. The cyclic AMP-elevating drug. forskolin. abrogated the ability of exogenous IL-2 to increase sIL-2Rα production. Thus, in the burn patient, the reduced in vitro sIL-2Rα release appears to relate to abnormalities in IL-2 production and action mediated through its functional surface receptor. Elevated levels of sIL-2Rαin vivo may, therefore, reflect systemic activation of T lymphocytes in response to biologically active IL-2.