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SBS2008 Exchange not sending SMTP email

For the last ~24 hours my SBS2008 server hasn't been sending SMTP email.

Users are receiving 'Delivery delayed' bounce emails after my 2hour send-fail threshold.

The backlog of emails is visible in Exchange Console Queue Viewer.  The full text of the error in ALL queues to various domains in the Queue Viewer is:
    "451 4.4.0 Primary target IP address responded with: "421 4.2.1 Unable
    to connect." Attempted failover to alternate host, but that did not succeed.
    Either there were no alternate hosts, or delivery failed to all alternate hosts."

I *am* able to receive SMTP email from the outside world.  And all email within the organisation is sending/receiving OK.

Web-browsing & all other internet access is OK.

The Exchange SMTP send connector is set to use the network adaptor for DNS resolution, and the network adaptor's DNS is configured to the private IP of this same SBS2008 server, & the SBS2008 DNS server's forwarders are set to OpenDNS.  This has been a stable config for 9 months.

I don't recall making any config changes that could account for this.

I'm using Symantec Endpoint Protection for antivirus & antispam filtering.

I've rebooted SBS, problem remains.

Any ideas?
Thanks, Anthony.
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James
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Thanks your your suggestion, it sent me back to basics, and I discovered my ISP had mistakenly blocked port25 outgoing, even though all such 'noob' filtering should have, and was indicated by them, to be turned off.

I enabled their filter, then disabled it, & my SMTP queues emptied within minutes.