Opportunistic infections and neoplasms of the anorectum have been reported in patients with human immunodeficiency virus (HIV) infection. More recently, idiopathic ulcerative lesions of the colon and rectum have been described. At our center over a 3-yr period, four patients were identified with ulcerative lesions of the rectum and/or anus that remained idiopathic despite an extensive clinical, serologic, and histopathologic evaluation. Three patients had the acquired immunodeficiency syndrome, and in one anorectal disease was the index manifestation of HIV infection. Only one of the patients had recently engaged in receptive anal intercourse. The presenting complaints were gastrointestinal bleeding in two, which was severe in one, and/or anorectal pain. Multiple colonoscopic evaluations with biopsy of the distal colorectum documented a solitary ulcer of the rectum in one, solitary ulcer involving the anorectum in two, and multiple ulcers of the rectum and anorectum in one. In three patients, colonoscopy to the cecum demonstrated no additional lesions. In patients with HIV infection, ulcerative lesions of the anorectum may remain unexplained despite an exhaustive evaluation. The etiology of these lesions, as well as appropriate therapy, remains to be determined.