The invention relates to a method for determining the responsiveness of a Dirofilaria spp. nematode to a macrocyclic lactone, by determining the genotype of the nematode at a position in a P-glycoprotein gene of the nematode corresponding to position 1 1, and optionally to position 618, in SEQ ID NO: 1, wherein the genotype GG at a position corresponding to position 1 1, or at positions corresponding to positions 1 1 and 618, in SEQ ID NO: 1 indicates that the nematode is likely resistant to the macrocyclic lactone. The invention also relates to methods for selecting a treatment to treat an animal infected with macrocyclic lactone resistant Dirofilaria spp nematode, and treating the animal; or for selecting a prophylactic to prevent an animal from becoming infected with a macrocyclic lactone resistant Dirofilaria spp nematode, and providing the prophylactic to the animal. The invention further relates to an isolated nucleic acid having at least 80% sequence identity to SEQ ID NO: 1.