Human colonic mucosal protection is not fully understood but may in part rely on a layer of mucus gel adherent to the mucosa. Ulcerative colitis may occur if mucosal protection breaks down. Two studies are presented, both of which relate to the aetiology of ulcerative colitis. First, a layer of adherent mucus gel was demonstrated by a simple, reliable method. Measurements of mucus layer thickness were made in freshly resected colonic specimens and shown to increase from a mean of 107 microns on the right colon to 155 microns in the rectum. In ulcerative colitis the layer is significantly thinner or absent, whereas in Crohn's disease the colonic mucus layer is significantly thicker. Second, the relationship between smoking and colitis is explored by a double-blind, randomised and placebo-controlled trial of transdermal nicotine in active disease. Significant clinical benefit was seen, indicating nicotine may be both useful therapeutically and the component of tobacco smoke that acts to protect against colitis. Since smoking and nicotine have actions on mucosae and mucus in other organs, it is argued that there is a mucus deficiency in ulcerative colitis that smoking acts to reverse.