I battled this for a good year.  The problem was excessive number of
mail queues (due to a lot of spam).

On any given day, my exchange front-end server, which communicates
in/out for all SMTP traffic to external hosts would have 500-700 queues
trying to delivery bad mail.  This was because the spam softare I had
worked at the mailbox level and not the gateway level.

The problem occurred only sometimes, and if a user got the error, they
could resend the mail 3 seconds later and it would go right through.  I
was talking to MS about other issues and asked about the relaying
problem.  They said that the number of excessive queues would likely
cause this problem.  No real explanataion as to why aside from the
server getting "confused" in SMTP communications, or something of that
nature.

I installed a Barracuda Spam Firewall at the gateway and it dropped my
average SMTP queue counts to 50-75 and the 5.7.1 relay errors
dissappeared, so MS was right.

-----Original Message-----
From: [EMAIL PROTECTED]
[mailto:[EMAIL PROTECTED] On Behalf Of Tony
Nguyen
Sent: Thursday, October 19, 2006 6:09 PM
To: Exchange Discussions
Subject: Still looking

I have on this for a week now and still looking for answer. Could
someone point me in the right direction please.

We receive email and it all come in just fine but when we do reply or
even a new email we get a 

smtp;550 5.7.1 Unable to relay
or
smtp;554 <[EMAIL PROTECTED]>: Relay access denied or smtp;550 5.1.1
<[EMAIL PROTECTED]>... User unknown

and sometime the reply go through email just fine and sometime it does
not.
I have checked the all the IIS and SMTP but everything look fine and
email is still flowing with some other domain just fine. Anyone have a
check list that I can use to trouble shoot this?

Thank
Tony

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