Although great strides have been made in the development of recombinant attenuated Vibrio cholerae vaccine strains, the task has not been as simple as once imagined. The initial vaccine candidates proved to be unexpectedly reactogenic but further derivatives, such as CVD103-HgR, are well-tolerated, immunogenic and protective after a single dose. In addition, this strain carries a selectable marker to distinguish it from wild strains and has been evaluated in a practical, lyophilized formulation (Levine et al., 1988b). While CVD103-HgR is being further evaluated in expanded trials, we are also investigating a new secretogenic factor which could possibly explain the diarrhoea seen with the earlier vaccine strains. Hopefully, these studies will achieve the long-sought goal of a safe and effective vaccine for the prevention of cholera.