It is clinically important to distinguish idiopathic inflammatory bowel disease (IBD) from other colitides, and ulcerative colitis (UC) from Crohn's disease (CD); however only a few histological criteria based on colonic biopsies have been established. We investigated 209 consecutive series of biopsies taken from 38 patients with UC, 12 with CD, and 105 with other colitides, to evaluate whether combinations of histological features, selected on the basis of our experience, and listed below, could be useful criteria for the differential diagnosis of IBD, and, more specifically, of UC: (A) chronic inflammation with a predominant increase of plasma cells, (B) crypt distortion, (C) crypt atrophy, (D) diffuse chronic inflammation within a biopsy and between biopsies, and (E) diffuse mucin depletion within a biopsy and between biopsies. Findings that fulfilled all or two of A-C distinguished IBD from the other colitides with high sensitivity (94.3%) and specificity (95.8%). When the findings fulfilled the additional criteria of D and/or E, UC was differentiated from CD or the other colitides with high sensitivity (86.4%) and specificity (99.3%).