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SMTP is based on end-to-end delivery: An SMTP client contacts the destination host's SMTP server directly, on well-known port 25, to deliver the mail. It keeps the mail item being transmitted until it has been successfully copied to the recipient's SMTP. This is different from the store-and-forward principle that is common in many mailing systems, where the mail item can pass through a number of intermediate hosts in the same network on its way to the destination and where successful transmission from the sender only indicates that the mail item has reached the first intermediate hop.

In various implementations, it is possible to exchange mail between the TCP/IP SMTP mailing system and the locally used mailing systems. These applications are called mail gateways or mail bridges. Sending mail through a mail gateway can alter the end-to-end delivery specification, because SMTP only guarantees delivery to the mail-gateway host, not to the real destination host located beyond the TCP/IP network. When a mail gateway is used, the SMTP end-to-end transmission is host-to-gateway, gateway-to-host, or gateway-to-gateway; the behavior beyond the gateway is not defined by SMTP.

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