Abstract Objectives: Interleukin-15 (IL-15) is a novel cytokine sharing many of the activities of IL-2. The goal of this study was to evaluate intracellular and serum IL-15 in ulcerative colitis (UC) and Crohn's disease (CD). Methods: Intracellular expression of IL-15 in peripheral blood mononuclear cells (PBMC) from UC patients, CD patients, and controls was studied using cell permeabilization and staining with monoclonal antibodies. Serum levels of IL-15 were detected using ELISA. Result: Percentage of IL-15 expressing PBMC was increased in UC patients and in five of six of CD patients with moderate and severe disease activity compared with controls. The number of IL-15 expressing cells in patients with active inflammatory bowel disease (IBD) declined within 2 wk of treatment. Serum IL-15 reached detectable levels in 62.5% of UC patients with moderate and severe disease activity but not in UC patients with slight disease activity or in remission, neither in CD patients nor in controls. In vitro lipopolysaccharide (LPS)-induced activation of PBMC from controls was associated with up-regulation of intracellular IL-15 expression (p < 0.01) and release of IL-15. Conclusions: UC patients with moderate and severe disease activity have increased percentage of IL-15 expressing PBMC, which might be induced by in vivo cell activation and can lead to elevation of released IL-15 in serum. Increased IL-15 expression after in vitro LPS stimulation of control PBMC suggests a nonspecific production of this cytokine during the immuno-inflammatory response.