In an investigation into alternative methods for the treatment and control of sheep scab, the efficacy of moxidectin, a second generation milbemycin, was evaluated in a series of laboratory and field studies in Ireland. Initial laboratory trials demonstrated that moxidectin, given as a subcutaneous injection at 200 μg/kg bodyweight was effective in the treatment of clinical psoroptic mange. Subsequent work showed that a single injection of clean sheep with moxidectin at the same dose rate provided protection against natural and experimental sheep scab infection for up to 35 days. This residual protective efficacy was tested in a large scale field trial in County Offaly, Ireland, in which more than 6500 sheep on 50 farms received a single prophylactic injection with moxidectin in the autumn and remained free from scab throughout the winter. This was comparable to the preventive effect of the annual compulsory dipping programme applied at that time. In a parallel series of field trials conducted across several counties in Ireland, two injections, 10 days apart, were effective in the treatment of outbreaks of scab. It is concluded that moxidectin is suitable for the treatment and control of sheep scab and has advantages over some existing methods because of its ease of use, safety for the user, the sheep and the environment, and because it also provides worm control owing to its efficacy against the major nematodes of sheep.