The present report describes the morphologic findings in sequential colorectal biopsy specimens obtained from 2 patients who within 1.5-2.5 yr developed collagenous colitis. The initial biopsy specimens revealed an acute nonspecific inflammatory reaction in the colorectal mucosa. An intermediate stage, characterized by edema and slight fibrosis in the subepithelial region of the colorectal mucosa, preceded the final development of collagenous colitis. We suggest that the mechanism that leads to the formation of a thick, bandlike subepithelial collagenous deposit in the colorectal mucosa may be triggered off by some inflammatory or toxic stimulus.