Aphis gossypii Glover causes direct and indirect damage to Cucumis melo L. crops. To decrease the harmful effects of this pest, one of the most economically and environmentally acceptable options is to use genetically resistant melon varieties. To date, several sources of resistance carrying the Vat gene are used in melon breeding programmes that aim to prevent A. gossypii colonization and the subsequent aphid virus transmission. The results suggest that the resistance conferred by this gene is associated with a microscopic hypersensitive response specific against A. gossypii. Soon after aphid infestation, phenol synthesis, deposits of callose and lignin in the cell walls, damage to the plasmalemma, and a micro-oxidative burst were detected in genotypes carrying the Vat gene. According to electrical penetration graph experiments, this response seems to occur after aphid stylets puncture the plant cells and not during intercellular stylet penetration. This type of plant tissue reaction was not detected in melon plants infested with Bemisia tabaci Gennadius nor Myzus persicae Sulzer.