Crohn's disease (CD) of the bowel showed a statistically significant thickening of the muscularis mucosae when compared with disease controls. In areas of gross stricture in CD, the muscularis mucosae comprised almost 10% of total wall thickness. Similar findings were also present in a previously characterized experimental model of CD (trinitrobenzene sulfonic acid-induced colitis in rats), particularly in what appeared to be grossly strictured areas. Taken together, these findings suggest that increased mass of muscularis mucosae smooth muscle may be responsible in part for the commonly observed stricture formation in CD. As extreme muscularis mucosae hyperplasia appears to be peculiar to CD, it may serve as an additional marker differentiating CD from other diseases.