This paper describes the present state of research on the pathogenicity of Escherichia coli and points out the gaps in knowledge that should be filled in the future. First, the great versatility of E. coli in producing disease is noted, as well as the invaluable contributions that studies of it have made to the development of general knowledge on bacterial pathogenicity. Then, the biological requirements for pathogenicity: infection of mucous surfaces; penetration of those surfaces; multiplication in vivo; interference with host defence mechanisms; and damage to the host, are taken in turn, and an enquiry is made on how far studies have progressed toward identifying their molecular determinants and relating structure to biological action. Only for mucous surface adhesins and protein toxins are studies at the structure-function level. Some progress has been made on interference with host defence, but little is known about competition with commensals on mucous surfaces, invasion into the tissues, and growth in vivo.