Predicting the magnitude of enemy release in host-pathogen systems after introduction of novel disease resistance genes has become a central problem in ecology. Here, we develop a general quantitative framework for predicting changes in realized niche size and intrinsic population growth rate after introgression of disease resistance genes into wild host populations. We then apply this framework to a model host-pathogen system targeted by genetically modified and conventionally bred disease-resistant host lines (Trifolium repens lines expressing resistance to Clover yellow vein potyvirus) and show that, under a range of ecologically realistic conditions, the introduction of novel pathogen resistance genes into host populations can pose a quantifiable risk to associated nontarget native plant communities. In the host-pathogen system studied, we predict that pathogen release could result in an increase in the intrinsic rate of population growth of up to 15% and the expansion of host populations into some marginal environments. This approach has general applicability to the ecological risk assessment of all novel disease-resistant plant genotypes that target coevolutionary host-pathogen systems for improvement of agricultural productivity.enemy release hypothesis ͉ genetically modified plants ͉ nontarget ecosystems ͉ risk assessment ͉ Trifolium repens U ntil relatively recently, it was thought that diseases were of little importance in most natural plant communities (1, 2), but now it is known that diseases can influence the genetic structure of host populations, the dynamics of host metapopulations, and even the physiognomic and floristic structure of entire natural plant assemblages (1, 3-5). Recent evidence also suggests that release from pathogen attack is at least partly responsible for the success of many invasive species worldwide (the enemy release hypothesis) (6, 7), and indeed several biological control programs owe their success to the suppressive effects of pathogens in weedy host populations (8). For these reasons, it has been suggested that novel pathogen-resistant plants may pose a major risk to the environment, because genes coding for pathogen resistance could result in population expansion and increased invasiveness of either the resistant plant itself or of sexually compatible nontarget species (9, 10). Certainly, the literature is replete with examples of crop protection by means of the introduction of disease resistance genes (11), but is this situation likely in natural systems, and under what conditions could it occur?Although it is clear that newly introduced pathogens can have devastating impacts on naïve host populations (1), surprisingly little information is available about the role of pathogens in shaping the demography of long-term coevolved host-pathogen systems, although effects are likely to be highly variable (1, 2). Moreover, detailed experimental case studies are few, particularly for understudied but numerically important pathogen groups such as viruses (9). Because a number of ...