The pathogenesis of segmental colitis associated with diverticula (SCAD) is unclear, but tumour necrosis factor alpha (TNF-alpha) has been shown to play a pivotal role in the pathogenesis of inflammatory bowel diseases. The aim of this study was to assess TNF-alpha levels in patients with SCAD. In a post hoc analysis of a prospective multicenter study, tissue samples from 13 patients diagnosed with SCAD were subjected to histological analyses. The severity of the inflammation was assessed by means of a histological score and histomorphometry (number of inflammatory cells/mm2). Immunohistochemical staining with an antibody against TNF-alpha was performed on all biopsies and the degree of staining expressed as the percentage of positive stromal cells/1000 counted (TNF-alpha score). Matched patients with irritable bowel syndrome (IBS) were used as controls. Over-expression of TNF-alpha was found in all SCAD patients (38.6 +/- 10.4%), and it was associated with a high histological score (2.5 +/- 0.5) and neutrophil cell count (16.3 +/- 3/mm2). These values were distinctly higher than those found in the IBS controls. Our data suggest that TNF-alpha activity is involved in SCAD pathogenesis, similarly to what occurs in Crohn's disease and ulcerative colitis.