Resistance to Aphis gossypii Glover (cotton-melon aphid) in melons is conferred by a dominant gene that causes an inhibition of feeding from the phloem sieve element. Biochemical comparisons between resistant and susceptible melon accessions have failed to reveal differences that account for the dramatic reduction in aphid performance caused by the resistance gene. Consequently, we are pursuing a molecular-genetic approach to analyze the resistance mechanism, including the construction of a genetic map of the A. gossypii resistance locus for which we propose the name Agr (Aphis gossypii resistance). A low resolution map of the resistance locus was constructed with RAPD and RFLP markers. Aphid resistance in melon is genetically linked to resistance to virus transmission and resistance to the powdery mildew fungus, raising the possibility that Agr resides in a cluster of resistance genes. Plant resistance gene clusters have been shown to harbor genes with conserved sequence motifs, including leucine-rich repeats (LRR) and nucleotide binding sites (NBS). We have isolated resistance gene-like sequences from the melon genome that are linked to Agr. These data support the hypothesis that Agr is a member of the NBS-LRR superfamily of plant resistance genes.