Twenty-two Rhesus monkeys were orally fed 1 x 10(11) live virulent Shigella flexneri of either serotypes 1b, 2a, 4a or Y. On the basis of colonoscopic findings they were classified into: group A - normal endoscopic picture (10 monkeys), and group B - pathological endoscopic picture (12 monkeys). Pathological findings, distributed over the entire colon, were seen as either red patches (+/- erosions) or diffuse lesions, i.e. fragile red mucosa, mucosal bleeding and broad edemas. Histopathological examination of concomitant biopsies showed an acute inflammation restricted to the mucosa in 8/12 of group B as compared to 2/10 of group A. The Shigellae were most commonly demonstrated in the surface epithelium and more rarely in the deep layer of the lamina propria. Immunohistochemical staining, using monoclonal antibodies directed against Shigella flexneri O-antigenic polysaccharide, showed a high correlation with histopathological findings. Clinically all 10 monkeys in group A remained healthy, whereas 7/12 (all displaying histopathological signs of acute inflammation) in group B developed dysenteric symptoms. Colonoscopy should be combined with histopathological and immunohistochemical examinations of biopsies to study the pathological events taking place in the colon tissue during the course of a Shigella infection and will be of great value to assess the protective efficacy of S. flexneri vaccine candidates.