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Background: In recent years, the euthanasia of seals has been discussed internationally and concern has been raised regarding the use of rifles, the effect of different calibres, and which calibres are sufficient for humane euthanasia. This study therefore investigated the effect of different firearm calibres on euthanasia of grey seals (Halichoerus grypus) in traps, and provides information for the development and refinement of regulations for hunting seals in the wild., Findings: The effect of different calibres was studied in 19 seals shot in the head and neck at close range. All seals were necropsied and radiographed to characterize the injuries caused by the bullets. All tested calibres, 5.6 mm bullet diameter or larger, and .12 shotgun, were sufficiently effective to cause severe skull fractures, meningeal haemorrhages and instant death., Conclusions: Rifles with 5.6 mm bullet diameter or larger, and a .12 shotgun loaded with a slug fired at close range to the head and neck of grey seals all caused instant death and can therefore be recommended for hunting seals in the wild.