Aphids and related insects feed from a single cell type in plants: the phloem sieve element. Genetic resistance to Acyrthosiphon kondoi Shinji (bluegreen aphid or blue alfalfa aphid) has been identified in Medicago truncatula Gaert. (barrel medic) and backcrossed into susceptible cultivars. The status of M. truncatula as a model legume allows an in-depth study of defense against this aphid at physiological, biochemical, and molecular levels. In this study, two closely related resistant and susceptible genotypes were used to characterize the aphid-resistance phenotype. Resistance conditions antixenosis since migratory aphids were deterred from settling on resistant plants within 6 h of release, preferring to settle on susceptible plants. Analysis of feeding behavior revealed the trait affects A. kondoi at the level of the phloem sieve element. Aphid reproduction on excised shoots demonstrated that resistance requires an intact plant. Antibiosis against A. kondoi is enhanced by prior infestation, indicating induction of this phloem-specific defense. Resistance segregates as a single dominant gene, AKR (Acyrthosiphon kondoi resistance), in two mapping populations, which have been used to map the locus to a region flanked by resistance gene analogs predicted to encode the CC-NBS-LRR subfamily of resistance proteins. This work provides the basis for future molecular analysis of defense against phloem parasitism in a plant model system.Parasitism by phloem-feeding insects, such as aphids and whiteflies, is a widespread and often serious constraint on plant production. Aphids have been especially successful in exploiting a broad range of vascular plants. In temperate regions, approximately one in four plant species can be colonized by at least one species of aphid (Dixon, 1998). Phloem feeders may harm plants by direct feeding damage and by vectoring microbial pathogens. These insects are exquisitely adapted to their hosts, feeding from a single cell type, the sieve element, at the plant interior. This cell-specific mode of herbivory presents both a technical challenge and an opportunity for plant biologists to elucidate ways in which plants defend against parasitism of the translocation stream.Despite the ubiquity of phloem feeding, basic knowledge of its relation to plant physiology and, in particular, to plant defense has lagged behind knowledge of plant-microbe interactions. This imbalance is starting to change, however, as molecular tools are applied to the study of induced responses to phloem feeding and to mechanisms of genetic resistance (for review, see Walling, 2000;Kessler and Baldwin, 2002;Moran et al., 2002). Studies with Arabidopsis (Arabidopsis thaliana) and cultivated species have identified changes in gene expression when plants are challenged with phloem feeders (Walling, 2000;Moran and Thompson, 2001;Moran et al., 2002;de Ilarduya et al., 2003;Zhu-Salzman et al., 2004). Considering the intimate and enduring contact of insect stylets with the host tissue, it is not surprising that these and other stud...