This is a study of first attacks of colitis, evaluating prospectively the overall course with repeated histologic, clinical, laboratory, and initial microbiologic examinations. Forty-two attacks of colitis could after a follow-up period of 5.5 years be separated into relapsing and non-relapsing types. Relapse was chosen as a prerequisite for a final diagnosis of inflammatory bowel disease. In the non-relapsing group 72% of the patients harboured enteropathogenic bacteria. An insidious onset of diarrhoeal symptoms was highly discriminant of inflammatory bowel disease, whereas an acute onset mostly occurred in patients with non-relapsing colitis. Macroscopic differentiation at sigmoidoscopy was not possible. Distorted crypt architecture (92%) and/or basal plasmacytosis (77%) at initial biopsies strongly indicated inflammatory bowel disease but was also found transiently in patients with infectious colitis (19%). Thus, careful microbiologic and clinical investigation and repeated histologic examinations are necessary to distinguish infectious colitis from inflammatory bowel disease.