It's random - and not to the ones we host. We host several Listservs and the majority of the errors are from that, but to valid domains. It also happened for one person internally sending to an outside domain.
In this case, you should take a look at the "SMTP" or "SMTP-" log file entries (the ones where the 421 message occurs) for a single E-mail that has this problem. That should help track down the problem (such as letting you know if IMail is connecting to the correct mailserver).
-Scott
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