I am seeing errors like:Status: 5.4.4 (Illegal host/domain name found). Almost all destinations have no A records, only MX records. The user can usually resend the message and it works.  Any ideas?

I do have MX in tcp_local in imta.cnf

The problem is not in the mail software, the problem is in your DNS system. 554 is a permenant failure which means that the MTA got an authoritative response from DNS reporting that the host/domain did not exist.
When the user tries again, the MTA queries again, and this time DNS responds with a positive response.
First see the NMS tuning guide and enable nscd, it might be related, not sure, can't hurt, will improve performance.
Your DNS server should be waiting until it gets a positive/negative response from the root servers. Sounds like that is not happening, maybe a timeout kicking in and causing it to return a authoritative answer (which is incorrect) and then on a subsequent query the response made it and thus the lookup works.

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