Classic malakoplakia was found in the colon of a patient with a 30-year history of proven ulcerative colitis. She had undergone total proctocolectomy after failure of medical treatment to control her illness. Immunoperoxidase studies showed immunoglobulins and muramidase within the malakoplakic histiocytes, and electron microscopy showed bacteria resembling Escherichia coli in the same cells. Immunologic studies on the patient showed an unusually high E coli antibody titer (1:512) in her serum and reduced numbers of circulating T-lymphocytes with reduced cytotoxic activity. This case shows the paradoxical rarity of malakoplakia in ulcerative colitis and reaffirms the presence of an immunologic defect that may be pathogenetically significant.