Acute graft-versus-host disease (GVHD) may affect several organs. Syndecan-1 is a heparan sulfate proteoglycan that can be shed from the surface of most epithelial cells (skin, liver, and gut among others), which are target organs for GVHD. Syndecan-1 was measured in serum samples from 60 patients after allogeneic stem-cell transplantation and was related to the degree of GVHD. Syndecan-1 levels increased in patients who developed acute GVHD but not in patients without GVHD. The difference between groups was significant 3 to 10 weeks after transplantation. The peak level of syndecan-1 in serum correlated with the degree of acute GVHD (r=0.46, P<0.001). Combined, the peak levels of syndecan-1 and soluble interleukin-2 receptor detected patients with acute GVHD (sensitivity 82%, specificity 89%). This study shows that syndecan-1 levels are increased during acute GVHD. Syndecan-1 may be a marker for acute GVHD, especially if combined with determination of soluble interleukin-2 receptor.