Hello All,

I am running MS Exchange 2010 with DAG environment, since couple of weeks my Users are receiving below errors while sending emails to few different domains 

xyz.com gave this error:
Please turn on SMTP Authentication in your mail client. :34464 is not permitted to relay through this server without authentication.

OR

xyz.com gave this error:

Please turn on SMTP Authentication in your mail client, or login to the IMAP/POP3 server before sending your message. :8852 is not permitted to relay through this server without authentication.

OR

xyz.com gave this error:

Relaying not allowed - REASON -

A problem occurred during the delivery of this message to this e-mail address. Try sending this message again. If the problem continues, please contact your helpdesk.

But after few retries message successfully send to destination.

There is also no changing activity performed in my Exchange Environment.

Hi 

Please Enable protocol logging and see if we get any additional information in the logs.

Try dropping an email through Telnet to the NDR domain and see if you get any errors in the transit

Hi,

According to your description, I understand that failed send message to few different domain with error Please turn on SMTP Authentication in your mail client, . is not permitted to relay through this server without authentication.
If I misunderstand your concern, please do not hesitate to let me know.

I want to double confirm whether all user or special account experience this question. Which mail client are they used, OWA, Outlook? And also check the Outlook account type?

Basic on the error message, its caused by they do not enabled SMTP Authentication in your email client.
If they use Outlook client with POP3\IMAP account, please make sure they have enable My Outgoing server (SMTP) requires authentication, also check the Outing mail Incoming port setting.
Additional, run below command to double check the configuration of IMAP and POP3:
Get-ImapSettings -server <CAS server name>
Get-PopSettings -server <CAS server name>

Thanks