Lymphogranuloma venereum (LGV), a sexually transmitted disease, is caused by certain immunotypes of Chlamydia trachomatis. Proctitis due to LGV may be histologically indistinguishable from Crohn's disease of the rectum, thereby creating a diagnostic and therapeutic dilemma. The pathologic features found at autopsy at The Johns Hopkins Hospital in the 28 patients in whom LGV had been diagnosed clinically were reviewed, with the clinical features, to determine whether any of those features could be used to distinguish between LGV and Crohn's colitis. The results showed that although many of the pathologic findings in the intestines of subjects with LGV were similar to those observed in patients with Crohn's disease, the distribution of lesions in the colons of subjects with LGV was distinctly different from that observed in patients with Crohn's colitis. With LGV, the salient histopathologic lesions consisted of follicular lymphohistiocytic-plasma cell infiltrates in the submucosa, muscularis propria, and serosa; neuromatous hyperplasia in the submucosal and myenteric plexuses; and extensive thickening and fibrosis of the bowel wall. The rectum was uniformly involved by these processes and, in addition, had deep ulceration and fissuring, while more proximal segments of the colon were generally spared of severe chronic inflammation. Thus, the colonic lesions of LGV have a distal left-sided predominance, in contrast to the usual right-sided predominance with rectal sparing in Crohn's colitis.