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In Solidity, `tx.origin` and `msg.sender` are two variables that serve different but crucial purposes. `tx.origin` always refers to the address that initially initiated the transaction and remains constant throughout the transaction chain. On the other hand, `msg.sender` represents the sender of the current message or contract interaction and changes with each call. It is crucial to be cautious when using `msg.sender`, as it may not always represent the initial caller of the transaction.