Seems I am always being asked about the actual meaning of the various cryptic non delivery reports generated by Exchange, This blog explains the meaning of the NDR Error Codes received in Non-Delivery reports. This information can be useful in determining the specific cause of the email delivery failure and indicates where to perform troubleshooting is needed.

4.2.2 The recipient has exceeded their mailbox limit. It could also be that the delivery directory on the Virtual server has exceeded its limit. (Default 22 MB)
4.3.1 Not enough disk space on the delivery server. Microsoft say this NDR maybe reported as out-of-memory error.
4.3.2 Classic temporary problem, the Administrator has probably frozen the queue.
4.4.1 Intermittent network connection. The server has not yet responded. Classic temporary problem. If it persists, you will also a 5.4.x status code error.
4.4.2 The server started to deliver the message but then the connection was broken.
4.4.6 Too many hops. Most likely, the message is looping.
4.4.7 Problem with a timeout. Check receiving server connectors.
4.4.9 A DNS problem. Check your smart host setting on the SMTP connector. For example, check correct SMTP format. Also, use square brackets in the IP address [197.89.1.4] You can get this same NDR error if you have been deleting routing groups.
4.6.5 Multi-language situation. Your server does not have the correct language code page installed.
5.0.0 SMTP 500 reply code means an unrecognised command. You get this NDR when you make a typing mistake when you manually try to send email via telnet. More likely, a routing group error, no routing connector, or no suitable address space in the connector. (Try adding * in the address space) This status code is a general error message in Exchange 2000. In fact Microsoft introduced a service pack to make sure now get a more specific code.
5.1.x Problem with email address.
5.1.0 Often seen with contacts. Check the recipient address.
5.1.1 Another problem with the recipient address. Possibly the user was moved to another server in Active Directory. Maybe an Outlook client replied to a message while offline.
5.1.3 Another problem with contacts. Address field maybe empty. Check the address information.
5.1.4 Two objects have the same address, which confuses the categorizer.
5.1.5 Destination mailbox address invalid.
5.1.6 Problem with homeMDB or msExchHomeServerName - check how many users are affected. Sometimes running RUS (Recipient Update Service) cures this problem. Mailbox may have moved.
5.1.7 Problem with senders mail attribute, check properties sheet in ADUC.
5.2.x NDR caused by a problem with the large size of the email.
5.2.1 The message is too large. Else it could be a permissions problem. Check the recipient's mailbox.
5.2.2 Sadly, the recipient has exceeded their mailbox limit.
5.2.3 Recipient cannot receive messages this big. Server or connector limit exceeded.
5.2.4 Most likely, a distribution list or group is trying to send an email. Check where the expansion server is situated.
5.3.0 Problem with MTA, maybe someone has been editing the registry to disable the MTA / Store driver.
5.3.1 Mail system full. Possibly a Standard edition of Exchange reached the 16 GB limit.
5.3.2 System not accepting network messages. Look outside Exchange for a connectivity problem.
5.3.3 Remote server has insufficient disk space to hold email. Check SMTP log.
5.3.4 Message too big. Check limits, System Policy, connector, virtual server.
5.3.5 Multiple Virtual Servers are using the same IP address and port. See Microsoft TechNet article: 321721 Sharing SMTP. Email probably looping.
5.4.0 DNS Problem. Check the Smart host, or check your DNS. It means that there is no DNS server that can resolve this email address. Could be Virtual Server SMTP address.
5.4.1 No answer from host. Not Exchange's fault check connections.
5.4.2 Bad connection.
5.4.3 Routing server failure. No available route.
5.4.4 Cannot find the next hop, check the Routing Group Connector. Perhaps you have Exchange servers in different Routing Groups, but no connector.
5.4.6 Tricky looping problem, a contact has the same email address as an Active Directory user. One user is probably using an Alternate Recipient with the same email address as a contact.
5.4.7 Delivery time-out. Message is taking too long to be delivered.
5.4.8 Microsoft advise, check your recipient policy. SMTP address should be cp.com. NOT server.cp.com.
5.5.0 Underlying SMTP 500 error. Our server tried ehlo, the recipient's server did not understand and returned a 550 or 500 error. Set up SMTP logging.
5.5.2 Possibly the disk holding the operating system is full. Or could be a syntax error if you are executing SMTP from a telnet shell.
5.5.3 More than 5,000 recipients. Check the Global Settings, Message Delivery properties.
5.5.5 Wrong protocol version.
5.6.3 More than 250 attachments.
5.7.1 Permissions problem. For some reason the sender is not allowed to email this account. Perhaps an anonymous user is trying to send mail to a distribution list. Check SMTP Virtual Server Access Tab. Try checking this box: Allow computers which successfully authenticate to relay. User may have a manually created email address that does not match a System Policy.
5.7.2 Distribution list cannot expand and so is unable to deliver its messages.
5.7.3 Check external IP address of ISA server. Make sure it matches the SMTP publishing rule.
5.7.4 Extra security features not supported. Check delivery server settings.
5.7.5 Cryptographic failure. Try a plain message with encryption.
5.7.6 Certificate problem, encryption level maybe to high.
5.7.7 Message integrity problem.

As always, comments welcome !