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Substitutions

Each team is allowed to substitute for any player at any time the ball is dead. A batter who replaces another batter is referred to as a pinch hitter; similarly, a pinch runner may be used as a replacement for a baserunner. Any player who replaces another player between innings, or while the team is in the field, is known as a "defensive replacement". A replacement pitcher is called a relief pitcher.
Any replacement is a permanent substitution; the replaced player may not return to the game under any circumstances. Thus, a pitcher that has been removed from the game and replaced by a relief pitcher cannot return to pitch later in the game, and any batter who is replaced by a pinch-hitter cannot take the field in the following inning (or even bat again if his turn comes up again in the same inning). Note however, that two players can switch defensive positions at any time, and both can still stay in the game—because neither has actually been removed from the game. This means that in at least one case, a pitcher switched positions with an outfielder in the middle of the game, with the outfielder becoming a relief pitcher ... then later in the game, the players switched back. This meant that in practical terms, the starting pitcher was relieved by another pitcher, but then came back to relieve the relief pitcher. This game took place on September 28, 1952: the players in question were starting pitcher Harvey Haddix, who moved to the outfield to make way for outfielder-turned relief pitcher Stan Musial, then switched back to pitcher after Musial had faced one batter. Note that this did not violate baseball's permanent substitution rule in any way, as at no time did either player leave the game.
This "permanent substitution" rule is in contrast to some other sports, such as basketball, hockey and American football, that practice "free substitution". In some cases, if the defensive manager responds to the entrance of a pinch-hitter by bringing in a new pitcher, the pinch-hitter may be replaced by another pinch-hitter without having even come to the plate, in which case the first pinch-hitter is considered to have entered the game and is ineligible to do so later. However, the defensive manager may not replace a pitcher who has not pitched to at least one batter, except in case of injury.
Many amateur leagues allow a starting player who was removed to return to the game in the same position in the batting order under a re-entry rule. Youth leagues often allow free and open substitution to encourage player participation.