SMTP 550 5.4.1: no answer from host (and the Microsoft meaning)
A 550 5.4.1 reply means the sending side could not get an answer from the destination host. RFC 3463 defines X.4.1 as "No answer from host". Microsoft Exchange and Microsoft 365 also return 5.4.1 when they reject a recipient or refuse to relay a message, so read the reply text to know which case you have.
The enhanced status code 5.4.1 is defined by RFC 3463 as "No answer from host": the sending server reached the routing stage but the destination host did not respond.
What the RFC meaning covers
The destination mail host is down, unreachable, or timing out.
A firewall or network route is dropping the connection.
DNS points at a host that never answers on port 25.
Why Microsoft servers say 5.4.1 for something else
Microsoft Exchange and Microsoft 365 reuse 5.4.1 with wording like "Recipient address rejected: Access denied". On those systems the code most often means the recipient does not exist or your server is not authorized to relay, not a network timeout. Read the full text of the reply to tell the two cases apart.
How to fix it
If the host is genuinely unreachable, confirm the MX records and that the target host answers on port 25. If you see the Microsoft "Access denied" wording, verify the recipient address and your relay or authentication permissions. Because the leading digit is 5, this is a permanent failure and the same message will not be retried automatically.
Common questions
Does 550 5.4.1 always mean a network problem?→
No. The RFC meaning is "no answer from host", but Microsoft Exchange and Microsoft 365 commonly use 5.4.1 for a rejected recipient or denied relay. Read the reply text.
Is 550 5.4.1 permanent?→
Yes. The leading 5 marks a permanent failure, so the same message will not be retried automatically.
How do I tell the network case from the Microsoft case?→
Check the text after the code. "No answer from host" points at a network or routing fault; "Recipient address rejected: Access denied" points at an address or relay-policy problem.
What should I check for a real no-answer-from-host failure?→
Confirm the MX records resolve, the destination host is up, and it accepts connections on port 25 without a firewall dropping them.