The astigmatid mite Psoroptes ovis (Acari: Proroptidae) causes the highly contagious and debilitating ovine disease, sheep scab. This ectoparasitic infection has a high economic and animal welfare impact on British sheep farming. Following recent work demonstrating resistance of Psoroptes mites to moxidectin, a widely used macrocyclic lactone (ML) treatment for scab, the current study compared the toxicity of three of the commonly administered macrocylic lactone therapeutic treatments (moxidectin, ivermectin and doramectin) to P. ovis from outbreak populations that had appeared unresponsive to treatment. These outbreak populations were from Wales and south west England. The data presented demonstrate that there is resistance to all three available ML compounds in populations of Psoroptes mites. However, considerable variation in response suggested that resistance alone was not responsible for the reported lack of efficacy in all of the submitted cases; lack of response in others may be associated with inappropriate treatment application or management. These data highlight the importance of the appropriate use of these compounds to manage national scab incidence at levels that are consistent with acceptable animal welfare standards, while attempting to reduce the development and spread of resistance.