Colitis is a life-threatening complication of aplastic anemia which occurs during periods of profound neutropenia. Four cases of this previously unreported association are described here. A syndrome of fever, watery diarrhea, and generalized abdominal pain and tenderness occurred in close temporal relationship to development of severe neutropenia (less than 50 neutrophils per cu mm). None of the patients had received antibiotics, nor had a history of previous episodes of colitis. Three had cultures positive for colonic organisms during the episodes. In only one instance was the correct diagnosis made without operation. Gross evidence of disease was found in the cecum, the transverse colon, and rectosigmoid in three patients, but the true extent of disease was underestimated. Microscopic examination of the two resected specimens showed extensive mucosal and variable submucosal necrosis with invasion of the colonic wall by bacteria. Acute inflammatory changes were absent. With profound neutropenia, the colon wall lacks resistance to invasion by the resident microflora. The condition is probably best treated without operation. If first recognized at laparotomy, resection should be avoided.