Substance P content was determined by radioimmunoassay in colonic mucosa from 24 patients with chronic severe constipation, 16 with active ulcerative colitis, and 28 normal controls. In patients with chronic severe constipation, the mean concentration of substance P (19.9 +/- 8.2 pg/mg) was significantly lower than in normal subjects (71 +/- 18 pg/mg). In patients with ulcerative colitis, colonic substance P concentration in inflamed mucosa (170 +/- 46 pg/mg) was significantly higher than its levels in normal subjects. Substance P may therefore have a role in the pathogenesis of clinical conditions associated with diarrhea and constipation.