Serum levels of soluble interleukin-2 receptors (sIL-2R), tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 were studied in patients who developed veno-occlusive disease of the liver (VOD) after allogenic bone marrow transplantation (BMT). sIL-2R increased by a mean of 366% in 10 VOD patients. This was significantly higher than in control patients (n=12) undergoing BMT without major complications (103%, P=0.002) or in patients (n=10) with grade II or III acute graft-versus-host disease (aGVHD) (139%, P=0.003). Peak sIL-2R levels occurred on day 17+/-4 (mean+/-SD) after BMT in VOD patients versus on day 29+/-11 in patients with grades II-III aGVHD (P=0.006), Mean maximum sIL-2R values in VOD patients were 4548+/-1420 (+/-SD, U/ml), which was significantly higher than the value of 2123+/-1023 U/ml in control patients undergoing BMT without major complications (P<0.001). In patients with grade II or III aGVHD, mean maximum sIL-2R levels were 3076+/-2264 U/ml. Serum levels of TNF-alpha, IFN-gamma, and IL-6 were also increased during VOD and aGVHD, with peak levels occurring at the same time as peak sIL-2R levels in most patients. We found no difference in peak levels between VOD and acute GVHD patients. To conclude, an early dramatic increase in sIL-2R was seen in patients with VOD. Inflammatory cytokines like IL-6, TNF-alpha, and IFN-gamma also increased during VOD and aGVHD.