The aim of this study was to examine the role of the olfactory system of the midge Culicoides imicola Kieffer as the major system mediating repellency to antihelminthic avermectins. Incidental observations indicate that treatment with Dectomax or Ivomec (commercial formula of the avermectins doramectin and ivermectin, respectively) protects sheep from infection by bluetongue (BT) viruses. Our electrophysiological data from midge antennae showed that the stimulating effectiveness of l-(+)-lactic acid, butanone, and sheep fleece odor decreased after addition of avermectins. The results show that these antihelminthics affect the olfactory sensitivity of the insect toward the animal host by reducing the response to those compounds that attract the insect, consequently reducing the possibility of biting the sheep and thereby transferring the BT virus.