Serum chromogranin A (CgA) levels have been reported to be normal, reduced or elevated in irritable bowel syndrome (IBS) patients. The aim of the present study was to establish a possible abnormality in CgA plasma level and in intestinal CgA cell density in IBS patients and to evaluate the outcome for the diagnosis of IBS. Forty-one patients with irritable bowel syndrome according to Rome Criteria III (39 females and 2 males; average age 35 years) and 59 healthy controls (37 females and 22 males; average age 45.5 years) were included in the study. Duodenal and colonic biopsies were obtained from all IBS patients. Forty-two of these healthy subjects underwent gastroscopy with duodenal biopsies. The remaining 17 subjects underwent colonoscopy with biopsies. The biopsies were immunostained with avidin-biotin-complex method for CgA cells. The cell densities were quantified by computerized image analysis. CgA plasma level was determined with ELISA technique. The density of CgA cells in both the duodenum and colon was reduced in patients with IBS. CgA cell density in the left colon was, however, unaffected in patients with IBS-constipation. There was no difference in the plasma level of CgA between patients with IBS and controls. The reduced density of intestinal CgA cells should be considered as a reduction in the total amount of intestinal endocrine cells. Which endocrine cell type is affected remains to investigate. This reduction may offer a histopathological test for the diagnosis of IBS. It is doubtful that the blood level of CgA has any clinical impact in IBS.