In American football, the neutral zone can be described as the length of the football from one tip to the other when it is spotted (i.e. placed on a certain spot) on the field during a scrimmage down and the area between the two free kick lines during a free kick down. For a scrimmage down, no member of either team, other than the snapper, may be in the neutral zone when the ball is snapped or a foul will be called. On a free kick down no member of either team except the holder and kicker may be in the neutral zone before the ball is kicked, nor can any onside kick be recovered by the kicking team until it has completely passed through the neutral zone.

Knowing whether the ball has passed beyond the neutral zone or remained in or behind the neutral zone is important during forward pass plays and during scrimmage kicks.

• "Behind the neutral zone" refers to the "offensive" side of the neutral zone.
• "In the neutral zone" refers to the actual neutral zone.
• "Beyond the neutral zone" refers to the "defensive" side of the neutral zone.

An additional definition of the neutral zone came into effect after a September 12, 2005, fight between the Philadelphia Eagles' Jeremiah Trotter and the Atlanta Falcons' Kevin Mathis that occurred prior to the opening kickoff. The NFL then instituted a rule that each end of the field from the end zone to the 45-yard line is reserved for one team, and that no player other than a kicker may be between the 45-yard lines prior to the game.

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