Soluble interleukin 2 receptors (S-R-IL–2) of truncated Tac chain, produced in vitro during T lymphocyte activation, may represent an in vivo marker of an alloimmune reaction. We analyzed serum S-R-IL–2 production during acute heart allograft rejection and compared soluble and membranous Tac chain (blood lymphocytes and graft invading cells) regulation during rejection. Serum S-R-IL-2 was tested in an immunora-diometric assay, with a combination of two mouse IgG1 anti-IL2-R mAbs (ART 18 and OX39). Membranous Tac chain was analyzed by immunochemistry in graft tissue, and by immunofluorescence on blood and spleen leuko cytes. Four experimental groups were used: untreated allogeneic, untreated syngeneic, CsA-treated (10 mg/kg/day for 15 days) allogeneic and CsA-treated syngeneic graft recipients. In the untreated allogeneic group, S-R-IL-2, tested every day until rejection (9.14±1.6 days), increased as early as day 3 after transplantation, peaked at day 6, and plateaued thereafter. The allograft was infiltrated at day.5 by Tac chain—positive cells (10% of OX1 cells and 84% of OX19 cells). A small percentage of mononucleated cells was labeled in blood, but not in spleen, by ART18 and OX39 at day 7 only. In contrast, in untreated syngeneic and CsA-treated allogeneic com binations, there was no increase of baseline S-R-IL-2 level (P< 0.001), and graft infiltrate did not contain IL-2-R positive cells. CsA treatment prolonged heart allograft survival (41.3±2.8 days). Baseline S-R-IL-2 levels during treatment were lower than those observed in untreated animals. In the CsA-treated allogeneic group, after CsA treatment interruption, S-R-IL-2 levels significantly increased, reaching a plateau at day 37. Results suggest that S-R-IL-2 measurement can be useful for clinical diagnosis of allograft rejection.