The adherence properties of non-fimbriate entero-invasive Escherichia coli O124 in the guinea pig intestinal tract were studied. Quantitative in-vitro determinations were done by incubating radiolabelled bacteria with suspensions of viable intestinal cells released by treating loops of the guinea pig intestine with solutions containing EDTA, dithiothreitol and citrate. Non-bound bacteria were separated from the intestinal cells on a Percoll gradient. Only cells released from the colon especially from its transverse and descending regions, avidly adhered to E. coli O124 (68-79 bacteria/cell), whereas the attachment to ileal cells was negligible. The adherence process was Ca++ and temperature-dependent, had an optional pH of 6.2 and was inhibited by fucose, glucose or mannose. Several pretreatment studies of the bacteria or the colonic cells showed that the adherence was mediated by a carbohydrate-binding protein (adhesin or lectin) on the colonic cells and not on the bacterial surface. Results of studies of in-vitro adherence to intestinal loops and to intact intestinal surfaces correlated well with the in-vitro findings. These results indicate that the adherence of entero-invasive E. coli O124 to the gut is similar to the attachement of Shigella flexneri and is quite different from that of enterotoxigenic E. coli.