Soluble interleukin-2 receptors (IL2R) were measured as markers of lymphocyte activation in serum and bile of liver transplant recipients. Serum and biliary levels were significantly higher in patients with acute rejection than in those with other complications (serum p less than 0.0025, bile p less than 0.001) or stable grafts (both p less than 0.0001). Levels rose 24 h before rejection could be detected by conventional liver tests. Biliary levels were more specific and sensitive than serum levels for rejection. Local production of IL2R accounted for the high levels in bile; the bile to serum ratio of IL2R was greater than that of albumin in 16 of 18 patients with acute rejection. Serum levels were high early in the course of chronic rejection but fell as it progressed to end-stage. Measurement of soluble IL2R may have a role in the early diagnosis of acute rejection and in identifying patients with chronic rejection in whom further immunosuppression will provide no benefit.