Background/Aims: Cytokines are thought to be important in mediating tissue damage in inflammatory bowel disease (IBD). Many of the in vivo activities of tumor necrosis factor α (TNF-α) match the changes found in IBD, but its importance is controversial. Methods: A sensitive, reverse hemolytic plaque assay was used to determine the frequency of TNF-α secreting cells isolated from mucosal biopsy specimens of children with Crohn's disease or ulcerative colitis (UC) and non-IBD controls before and after medical treatment. Results: Frequency of TNF-α secreting cells was significantly increased in biopsy specimens from children with mild, nonspecific inflammation compared with those with histologically normal intestine. Frequency did not increase in UC compared with children with nonspecific inflammation but was significantly greater in Crohn's disease than in UC. After treatment, the frequency of TNF-α secreting cells was reduced in patients receiving cyclosporin A, not reduced in patients with steroids or enteral nutrition, and not changed with treatment in UC. Conclusions: TNF-α secreting cells are increased in the mucosa of inflamed intestine, regardless of pathogenesis. In patients with IBD, higher levels are seen in Crohn's disease than in UC, probably reflecting the extensive T-cell activation in Crohn's disease. No relation existed between histological healing and the frequency of TNF-α-secreting cells.