A colleague of mine was fighting with CRM 4.0 at a client side. He was able to fix all their issues except one. They had changed from HTTP to HTTPS after installation and from that point on no one could connect externally. Anytime you changed something in the Outlook client the response was “The underlying connection was closed: an unexpected error occurred on a send.”. Not that much information to work with so I helped him to get the issue fixed. We dug through some log files to get some more information and found out that it was actually the audit plugin/service which was complaining with “the handshake failed due to an unexpected packet format”. Which clearly indicated it was something with the certificate or a specific HTTPS issue. Long story short, you need to change a registry value from port 80 to 443. We found all the necessary information on these sites: