The Rio Negro and Neuquén Valley is the most important apple and pear growing region in Argentina. Cydia pomonella L. (Lepidoptera: Tortricidae), the main fruit-tree pest is being controlled by azinphosmethyl (AzMe), acetamiprid (Acet), and thiacloprid (Thia) among other insecticides. The objective of this study was to evaluate the response of neonate larvae of codling moth to these three insecticides and on the role of cytochrome P450 monooxygenase in their toxicity. All field populations presented significantly lower mortality to a discriminating concentration (DC) of Acet and AzMe. In addition, 13 of the 14 populations showed significantly lower mortality to DC of Thia. Most of the field populations (71%) showed significantly higher 7-ethoxycoumarine O-deethylase activity compared with the laboratory-susceptible strain. While positive significant correlation (r = 0.59) was found between Thia and AzMe mortalities at the DC level, no significant correlations were detected between Acet and Thia (r = 0.35) or Acet and AzMe (r = 0.12). However, Acet and Thia mortalities were significantly correlated to the percentage of individuals exhibiting 7-ethoxycoumarine O-deethylase activity activities higher than the mean upper 95% confidence limit of the susceptible strain (r = -0.52 and r = -0.63, respectively).