The distribution of and morphological changes in substance P containing nerve fibers were examined immunohistochemically in the colonic mucosa of ulcerative colitis (UC) patients. Quantitative and morphological changes in substance P fibers were analyzed by digitized morphometry. The linear density of substance P fibers was significantly greater in the UC group (19.4 +/- 1.2 microns/1000 micron 2) than in the Crohn's disease group (10.1 +/- 1.2 microns; P < 0.01) and the control group (8.4 +/- 0.8 microns; P < 0.01). Analysis of the UC group showed that the degree of inflammation affected the linear density of substance fibers, with "moderate" cases presenting the highest linear density and "severe" cases the lowest. Substance P fibers were thickened and coarse in UC; they were significantly wider in the UC group (2.5 +/- 0.5 microns) than in the Crohn's disease group (1.5 +/- 0.2 microns; P < 0.01) and the control group (1.2 +/- 0.1 microns; P < 0.01). In conclusion, alterations in substance P containing nerve fibers, as evidenced by both the linear density and morphology, may play some role in the pathogenesis of UC.