Severe graft-versus-host disease (GvHD) of the gut clinically resembles Crohn's disease and ulcerative colitis. As low plasma levels of factor XIII (FXIII) have been described in chronic inflammatory bowel disease (CIBD) and as beneficial effects of FXIII concentrates in CIBD have been reported, we studied the FXIII plasma activity levels in patients undergoing allogeneic stem cell transplantation (SCT). In 20 of 22 patients with an uncomplicated course of SCT, FXIII stayed within the normal range (median 102 iu/dl, range 74-122), but was significantly reduced with the lowest FXIII levels on d 0 and 7 (d 0: median 83 iu/dl, range 55-165, d 7: median 83, range 70-101). In 20 of 22 patients with histologically proven GvHD of the gut, FXIII levels far below the normal range were observed (median 50, range 21-87) with a strong correlation between FXIII activity levels and degree of GvHD (r = -0.908; P < 0.001). We conclude that FXIII is consumed in patients with GvHD of the gut. As FXIII plays a a crucial role in haemostasis and wound healing, a study on the potential benefit of FXIII substitution in patients with severe GvHD of the gut might be rewarding.