Exchange server being used as an open relay

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Exchange is vulnerable to SMTP open relay in its default state after install. If your queues are backing up when there is no "normal" client traffic, then I suspect that your machine is being used for relay by a third party. If this is the case, your IP address and domain may very well be blacklisted.

Refer to Microsoft KB article 324958 for more information on how to lock down your SMTP gateway.

I would also suggest checking with http://www.ordb.org/faq/ for more information on this.