Recent studies suggest that patients identified by the Rome III criteria for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) are not distinct groups. Previous studies have shown that patients with IBS-C exhibit no or limited 5-HT response to meal ingestion, with plasma concentrations remaining similar to those under fasting conditions. The aim of this study was to determine whether patients with FC show a similar 5-HT response to meal ingestion as patients with IBS-C, and to investigate any relationship to gastrointestinal transit and visceral sensitivity. 23 female IBS-C patients, 11 female FC patients and 23 healthy female volunteers (HV) were recruited. Platelet depleted plasma 5-HT concentrations were measured under fasting (2hrs) and fed (4hrs) conditions. Within 2 weeks, oro-caecal (hydrogen breath test) and colonic (radio-opaque markers followed by X-ray) transit, along with rectal sensitivity (barostat) were determined. The main findings of the study are: 1. The FC patients had no 5-HT response to meal ingestion, as previously seen in patients with IBS-C, compared with healthy volunteers. 2. Patients with FC had abdominal and bowel movement associated symptoms as well as delayed colonic transit (whole gut transit), similar to that seen in IBS-C compared with healthy volunteers.3. The mean pain threshold in patients with FC was similar to that seen in healthy volunteers, with more patients with hyposensitivity or insensitivity in this group compared with IBS-C and no patients with hypersensitivity.4. Patients with FC had a shift towards higher fasting and postprandial PDP 5-HT levels, unlike patients with IBS-C, compared to healthy volunteers.This study show that based on symptoms, IBS-C and FC patients have more similarities than differences. However, although patients with FC had a similar 5-HT response to a test meal, they had different fasting 5-HT levels and some different physiological findings on assessment of visceral sensitivity with barostat.