We normally run with GWIA sending outbound mail to the ISP's relay host. This works ok. We are planning to change to a different ISP who do not provide a relay host (they say it is no longer standard practice and we should send direct to recipient). I tested by deleting the relay host setting from GWIA in C1 and mail stops being sent (piles up in DEFER).

Our setup is 8.0.2 hp3 on Win2008r2. Single server with POA/MTA/GWIA.

Logs look like this:
21:36:18 DB4 DMN: MSG 88302 Sending file: D:\domain\wpgate\GWIA\send\pee51b21.001
21:36:18 DB4 DMN: MSG 88302 No MX records found
21:36:18 DB4 DMN: MSG 88302 Attempting to connect to xxxx.co.uk
21:36:24 DB4 DMN: MSG 88302 xxxx.co.uk connection failure (8908)
21:36:24 DB4 DMN: MSG 88302 Send Failure: 450 Host down (xxxx.co.uk)
21:36:33 E5C MSG 88302 Analyzing result file: D:\domain\wpgate\GWIA\result\ree51b21.001
21:36:33 E5C MSG 88302 Detected error on SMTP command
21:36:33 E5C MSG 88302 Command: xxxx.co.uk
21:36:33 E5C MSG 88302 Response: 450 Host down (xxxx.co.uk)
21:36:33 E5C MSG 88302 Deferring message: D:\domain\wpgate\GWIA\defer\see51b21.001

This problem occurs on all outbound destinations when sending direct (and not at all when using relay host). I have confirmed that the destination domains have mx records and that the server can ping them by name and number. I have confirmed I can ping local DNS (another W2008r2/AD), I ave also confirmed I can telnet to the destination server refered to in the mx records at port 25 and run a manual SMTP session.

So this is not local DNS, not remote MX record configuration, and not firewall blocking SMTP outbound to those destinations.

I have also tried TID7008142 and 7005218.