Summary Salmonella Typhimurium strain GM3, known to be histotoxic for explants of terminal rabbit ileum in vitro, produces similar lesions in vitro when sterile filtrates, obtained from live organisms after interaction with gut explants in vitro, are used and when rabbit ligated ileal loops are challenged with live organisms. Epithelial damage occurs rapidly, within 2 h of adding organisms or sterile filtrates. This evidence is construed in terms of a secreted salmonella histotoxin that causes epithelial damage, detaching enterocytes which rapidly degenerate into spheroid cells devoid of microvilli. Typhimurium strain GM3 invades ileal mucosa and bacteria are found in the subepithelial tissues. After 12 h, bacteria were seen to be expelled from infected villi in a manner similar to that seen in non-histotoxic infection with Typhimurium strain TML.