Risk evaluation of genetically modified microorganism (GMMO) in relation to human health effects brings into consideration the ability of the microorganism to survive and colonise the gastrointestinal tract and the potential gene transfer to the resident microbiota. Different biological containment systems based on the activation of a killing gene have resulted in the reduced survival of the contained Escherichia coli or in the prevention of plasmid transfer between E. coli in the gnotobiotic rat. Gene transfer between Lactococcus lactis strains has been demonstrated in the gastrointestinal tract of gnotobiotic rats. The plasmid pLMP1 containing a selectable marker of a I!,. lactis strain was not transferred. The use of germ-free rats has led to a reduction in the number of laboratory animals needed for obtaining information regarding the fate and effect of GMMO in the mammalian gastrointestinal tract.