Three basic histopathological patterns which may be seen in rectal biopsies from patients with pseudomembranous colitis are described, based on a study of 29 cases. The spectrum of change is illustrated and the problems of differential diagnosis are discussed--from a non-diagnostic proctitis at one extreme to acute ischaemia at the other. In the differential diagnosis of the acute colitic, the importance of urgent rectal biopsy and a carefully taken drug history is stressed. The association of pseudomembranous colitis with pre-existing disease and antibiotic therapy is confirmed. It is suggested that these cause local mucosal damage and may trigger the first part of a local Shwartzman reaction. Capillary microthrombosis may then paly a part in producing the mucosal necrosis seen later in the disease.