Recipient Status 550 #5.1.0 Failures on Automatic Replies Only

I have a strange issue with regard to at least one of my users auto reply's.  This user is able to communicate with a particular client via normal emails without issue, but when she sets her Out of Office Assistant her auto reply's get bounced back
with the following Recipient Status: "550 #5.1.0 Rejected by bounce verification."   This only seems to happen with a few domains.  Is this an issue on the target side, or do I have some configuration issue to look into?  At first
I thought it was on their end, but since I can see it happening with more than one recipient at different domains I'm questioning my config.   

Hi MoltenArrow,
From your description, you can configure the third party Spam AV/Smart host to accept messages with empty return path for troubleshooting.
What's more, I recommend you use Test E-mail AutoConfiguration to check AutoDiscover on your problematic user's Outlook and normal user's. Compare the two result and check if there are any difference.
If the issue persists, please move the problematic user's mailbox to another database and see the result.
Here are some threads for your reference.
Auto Reply - OOO Not working - MS Exchange 2010
http://social.technet.microsoft.com/Forums/en-US/93edc530-2bb3-4036-a5d5-e7cfb51fc6fd/auto-reply-ooo-not-working-ms-exchange-2010
Auto Replies (Out of Office) not working - Exchange 2010 with Autodiscover running properly
http://social.technet.microsoft.com/forums/exchange/en-US/0cdd8ef4-f66e-491c-8c39-6790f0814f59/auto-replies-out-of-office-not-working-exchange-2010-with-autodiscover-running-properly
Hope it helps.
If there are any problems, please feel free to let me know.
Best regards,
Amy
Amy Wang
TechNet Community Support
HI Amy,
Thank you for the options, but I'm not sure you understood my question, or I didn't present it well.  We're not having trouble receiving, but sending.  There's no third party application at play.  Autodiscover
for this user is typical.  Their auto replies are going out to most  The message in the subject is the one that is returned, I'm assuming, by the target (external) server. 
Lrok and Bobby,
There is no NDR...  It just gets dropped.  That could be a function of our configuration as well, but I haven't confirmed that yet.  What I HAVE confirmed is that for ALL OOF replies the "Return-Path" header
is set to "<>" which is consistent with the error message I'm seeing.  When a normal email is sent that header is populated with the sender's address. (I'm checking this from an external email system)  I've practiced some Google-Fu on this
and it seems like that is the desired behavior since Exchange 2007 to prevent automated email storms, and is RFC compliant.  Can anyone confirm this?  **note: I'm using a single Exchange 2010 SP2 server with just a Hub transport, no Edge**
As for the Transport rule, I tried creating one but it didn't seem to affect it.  I didn't restart the server though, is that required for it to take effect?  Furthermore, If I follow the links provided I get references for Transport Agents and
Transport Rules, which I understand to be different things. Can anyone clarify that? Thanks!

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