Applications of Madex® (granulovirus) against the codling moth, Cydia pomonella, which targets neonate larvae before or during their initial entry into fruit, provide selective control of this key apple pest. Differences in the efficacy of Madex® treatment against C. pomonella larvae were observed in an experimental orchard in northern Italy on two apple tree cultivars, ‘Golden Delicious’ and ‘Red Chief’. The intensity of egg-laying by the moth may vary from one cultivar to another. The composition of a metabolite blend on the leaf surface consisting of glucose, fructose, sucrose, sorbitol, quebrachitol and myo-inositol is one of the factors that could explain these variations. Our hypothesis was therefore that variations in the efficacy of Madex® could be related to variations in egg numbers, itself related to the composition of metabolites on the leaf surface of each cultivar. Differences in egg-laying (number and localization) were recorded on the two cultivars, ‘Golden Delicious’ and ‘Red Chief’, untreated or treated with the larvicide. Madex® had the same efficacy on both cultivars in terms of the reduction of fruit damage due to larval feeding. Surprisingly, the effect of Madex® on reducing damage seemed less tied to a lethal effect of the larvicide on the larvae than to egg-laying reduction, the latter being linked to changes in chemical signals of the leaf surface induced by applications of Madex®. This observation was verified by experiments on egg-laying on an artificial substrate. When the active metabolite blends mimicking the corymb leaf surface compositions of each cultivar (untreated and treated with Madex®) were applied to nylon cloth egg-laying substrates, significant reductions in acceptance (% of egg-laying females) and egg-laying stimulation (number of eggs per egg-laying female) were observed. The reduction of eggs on ‘Red Chief’ could be primarily explained by a drastic effect on egg-laying stimulation, whereas the reduction on ‘Golden Delicious’ was partly due to a lower acceptance. The number of eggs laid naturally differs from one apple tree cultivar to another. The effects of reduced egg-laying caused by applications of Madex® were due to biochemical changes in surface blends, depending on the cultivar.