There is a low prevalence of smoking in ulcerative colitis. The disease often starts or relapses after stopping smoking. Increased intestinal permeability for harmful substances has been proposed as one causal factor in ulcerative colitis. We therefore wanted to study the relationship between smoking and intestinal permeability in healthy subjects. In 25 smoking and 25 non-smoking healthy persons urine recoveries of two different oral probes, 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) and low-molecular-weight polymers of polyethylene glycol (PEG 400), were measured. The smokers had significantly lower 24-h urine recoveries of 51Cr-EDTA than the non-smokers (median, 1.6; range, 0.8-4.2, versus 2.1; range, 1.1-5.8; 2 p less than 0.001). In contrast, 6-h urine recoveries of PEG 400 were not significantly different in smokers and non-smokers. Thus, smoking appears to tighten the gut either by effects on the paracellular junctions in the intestinal epithelium or by decreasing the permeability in the distal small bowel and the colon.