Crohn's disease (CD) and ulcerative colitis (UC) represent clinically distinct chronic inflammatory bowel diseases (IBD) of unknown etiology. Although the mucosal immune system is implicated in their pathogenesis, immunological differences between the two disorders are not well defined. The aim of this study was to compare in vitro mucosal T-lymphocyte function in CD and UC. Peripheral blood mononuclear cell interleukin-2 (IL-2) production was similar in pediatric IBD and control patients under unstimulated conditions, but was significantly increased in response to phytohemagglutinin (PHA) stimulation for the UC group. Lamina propria mononuclear cells (LPMNC) isolated from colonic resections in IBD patients had significantly lower spontaneous proliferation and IL-2 production in vitro than did LPMNC of control patients. In contrast, significantly greater IL-2 production was detected when the LPMNC of CD patients were cultured with PHA, in comparison with those of UC or control patients. When indomethacin, a prostaglandin synthetase inhibitor, was added to the cultures, significantly increased IL-2 secretion was observed for CD LPMNC, but not for UC cultures, under both stimulated and unstimulated conditions. These findings demonstrate abnormal LPMNC IL-2 production in IBD. Furthermore, our data suggest that inhibition of the prostaglandin synthetase pathway upregulates IL-2 production by LPMNC in CD. These results support the hypothesis that immunoregulatory mechanisms controlling IL-2 production differ between CD and UC.