Slow transit constipation (STC) is a disorder of intestinal motility of unknown aetiology. Myopathies, including those characterized by the finding of inclusion bodies, have been described in enteric disorders. Amphophilic inclusion bodies have been reported in the muscularis externa of the colon of STC patients. This study formally tested the hypothesis that these represent a primary muscle disorder, specific to STC. In a systematic, blinded, dual observer qualitative and quantitative analysis, colonic and ileal tissue from patients with STC (n=36) were compared with selected control populations: total colonic aganglionosis (n=10), Chagas' disease (n=6), isolated rectal evacuation disorders (n=6), and a control population of a range of ages (n=80). All sections were stained with haematoxylin and eosin and periodic acid Schiff. Further immunostains were used in an attempt to determine inclusion body composition. Round or ovoid (4-22 microm diameter) amphophilic inclusions increased in number in normal subjects with age. Inclusions were more frequent in idiopathic STC than in age-matched controls or rectal evacuation disorders [ileum (33% vs. 9%), ascending (50% vs. 19%, p<0.05), and sigmoid colon (43% vs. 20%)] and were very frequent in the sigmoid (71%) of patients with STC arising after pelvic surgery. The number of inclusions per unit area was significantly higher in patients with STC (p<0.001). Inclusions were found in all Chagas' patients, but not with aganglionosis. It was not possible to determine inclusion body composition, despite the use of a wide range of conventional and immunostains. This study demonstrates that inclusion body myopathy is identifiable in patients with STC and that it may arise secondary to denervation.