To examine the morphology of colitis and study the role of the immune system in colitis, we compared colitis in immunocompetent Wistar-Kyoto rats with that in spontaneously hypertensive rats, known to have T-cell dysfunction. Rats were treated with 3% dextran sulfate in drinking water for periods ranging from 3 to 60 days. Diarrhea developed earlier and was associated with a more severe weight loss in Wistar-Kyoto rats than spontaneously hypertensive rats. The morphologic findings (flattening of the gland epithelium, gland dropout and ulceration) in spontaneously hypertensive rats were milder than in Wistar-Kyoto rats. Only spontaneously hypertensive rats survived 60 days of treatment; the findings included ulceration, crypt distortion, and inflammatory pseudopolyp formation. Immunostaining for B-cell, T-cell, and macrophage markers showed no difference in the distribution of these cells in the mucosa of Wistar-Kyoto rats and spontaneously hypertensive rats. Spontaneously hypertensive rats with T-cell dysfunction develop dextran sulfate sodium-induced colitis.