Sending an email to user on same domain but hosted on another system

I need to be able to send emails to users of the same domain, but where their mailbox is hosted by a different (non-Exchange) system.

I've attempted it but got the usual "The email address you entered couldn't be found. Please check the recipient's email address and try to resend the message. If the problem continues, please contact your helpdesk."

Is there something I can set up in ECP?

Roger