Elevated expression of interleukin (IL)-18 mRNA and protein in intestinal mucosa, attributable to activated monocytes and macrophages in that site, has been reported in patients with inflammatory bowel disease (IBD). However, changes in serum IL-18 concentrations in patients with IBD have not been reported. We measured bioactive IL-18 in serum from patients with IBD, using an enzyme-linked immunosorbent assay (ELISA). Mean serum IL-18 concentrations in 5 patients with Crohn disease (CD) were 400 pg/mL, approximately 1.7 times higher than concentrations in 21 control subjects (p < 0.01). However, serum IL-18 was not increased in patients with ulcerative colitis (UC). These results suggest that like other T-helper type 1 (Th1) cytokines IL-18 may play a key pathogenetic role in Th1-mediated disorders, such as CD. Regulation and expression of IL-18 appears to differ between CD and UC, and serum IL-18 may be a useful clinical marker for CD.