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大学毕业后,莎莉(梅格·瑞恩 Meg Ryan 饰)开车载哈利(比利·克里斯托 Billy Crystal 饰)前往纽约,二人聊得并不愉快。哈里认为男女之间不可能有真正的友谊,萨莉却不以为然,于是不欢而散。5年后,二人又在飞机上巧遇,这时他们都有了意中人,但观点却没有改变,再次不欢而散。当又有一个5年后,二人再度重逢,都因感情出现了危机而有了共同语言。他们彼此安慰,临睡前通话,共度圣诞,为对方的感情出谋划策,哈利与莎莉有着不可言喻的默契。然而,这真的是一段伟大友谊的开始吗?
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