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During 2007, a large-scale controlled, multicentre, blinded and randomised field study was conducted in Scotland, England and France to assess the efficacy and safety of monepantel, the first molecule to be developed from the recently discovered amino-acetonitrile derivatives class of anthelmintics, in sheep. Monepantel was administered orally, at a minimum dose of 2.5 mg/kg bodyweight, for the control of gastrointestinal nematodes in sheep maintained at pasture in a range of commercial production systems. Efficacy was measured by faecal egg count (FEC) reduction tests seven days after treatment and was demonstrated to be over 98 per cent against mixed-genus infections. The reduction in FEC of monepantel-treated sheep was statistically significantly greater than in untreated control sheep (P<0.0001). The efficacy of monepantel against mixed-genus natural field infections of the major gastrointestinal nematodes was in agreement with similar studies conducted in Australia and New Zealand. There were no treatment-related adverse events during the study, which included the use of a range of concomitant treatments.