Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin (IL)-6, which may display antitumor activity. We evaluated sIL-6R and IL-6 levels in the sera of 24 patients following transplantation (allogeneic, n=17; autologous, n=7). Five patients developed acute graft-versus-host disease (AGVHD), three had early graft rejection, and three had an early relapse following bone marrow transplantation (BMT). Soluble IL-6R levels were evaluated at day -10, day 0, day of engraftment, and during BMT-related complications, using IL-6R- specific monoclonal antibodies (mAb) and double-sandwich ELISA. In normal controls, sIL-6R and IL-6 levels were 20±3 ng/ml and 0.01±0.005 ng/ml, respectively. Soluble IL-6R levels increased in direct correlation with engraftment in the uneventful allogeneic transplants (17.7±2.1 ng/ml at day 0 to 49.7±2.6 ng/ml at day of engraftment, n=6, P<0.05) as well as in the autologous transplants (26.8±2.82 at day 0 to 66.4±12.9 at day of engraftment, n=5, P=0.01). In contrast, IL-6 levels declined with time during the conditioning period and showed only a modest elevation following BMT. Increased levels of sIL-6R and IL-6 were found in the patients who developed AGVHD (23.8±4.2 and 0±0 ng/ml at day 0 to 79±6.9 and 0.26±0.04 ng/ml, respectively, at time of AGVHD, n=5, P=0.01). No correlation was found between the severity of AGVHD and sIL-6R levels. In the three patients with early relapse, sIL-6R levels increased from 30±0 ng/ml at day 0 to 90 ng/ml (P=0.05) and IL-6 levels increased from 0 to 0.16±0 ng/ml, respectively. The mean elevation of sIL-6R in the patients with early relapse and AGVHD was significantly higher than the mean elevation in the patients with the relatively smooth engraftment (P<0.05). Contrary to these findings, in the three patients with Kraft rejection, sIL-6R levels decreased while IL-6 was found to be elevated. Basic disease, conditioning regimen, type of transplant, GVHD prophylaxis, and T cell depletion had no effect on sIL-6R or IL-6 levels. In summary, sIL-6R levels positively correlated with engraftment. Both sIL-6R and IL-6 levels were found to be significantly elevated in patients who developed AGVHD or early relapse following BMT. Therefore, the sIL-6R level may be used as a tool for assessing engraftment and transplant-related complications following BMT.