Terminal ileal biopsies were prospectively obtained and stained specifically for mast cells in 20 patients with irritable bowel syndrome (IBS) and 15 controls. The number of terminal ileal mast cells per high powered field (MC/HPF) (mean +/- SEM) was 23.3 +/- 3.1 for IBS and 6.8 +/- 1.1 for controls (P = 0.0001). The diarrhea IBS subgroup had the greatest number of MC/HPF. No correlation was found between terminal ileal mucosal mast cell counts (MMCC) and the number of Manning criteria present or the functional bowel disease score (r = 0.06 and r = -0.31, respectively). We conclude that terminal ileal MMCC are significantly elevated in a majority of patients with IBS. The mast cell may be responsible for the altered visceral perception found in the gastrointestinal tract in patients with IBS. The poor correlation of the MMCC to the clinical features of IBS may be the result of the dynamic state of the mast cell.