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Background: Resistance to insecticides has been related to application history, genetic factors of the pest and the dynamic within the treated area. The aim of this study was to assess the geographic variation in azinphos-methyl response and the role of esterase and cytochrome P450 monooxygenase enzymes in codling moth populations collected within different areas of the Río Negro and Neuquén Valley, Argentina., Results: Diapausing field-collected populations showed resistance ratios at the LC(50) that were 0.7-8.7 times higher than that of the susceptible strain. Mean esterase (EST) and cytochrome P450 monooxygenase activities (expressed as α-N min(-1) mg(-1) prot(-1) and pg 7-OHC insect(-1) min(-1) respectively) were significantly correlated with LD(50) values from the field-collected populations. In addition, azinphos-methyl response was associated with the geographic area where the insect population was collected: populations from isolated and more recent productive areas presented significantly lower resistance ratios in comparison with populations from older and more intensive productive areas., Conclusion: The populations assayed presented different resistance levels to azinphos-methyl. The response was highly correlated with the orchard's geographic location. EST and ECOD activities were involved in azinphos-methyl response in the given region., (Copyright © 2012 Society of Chemical Industry.)