SMTP traffic loadbalancing originating from one IP - possible packet loss?

I think you might be misinterpreting what Colin and Jason are saying. There is no special virtual server or persistence configuration required - this is how TCP connections inherently behave. When your mail client wants to send a message, it first establishes a TCP connection with the virtual server. Then the LTM picks a pool member and opens up a corresponding TCP session with it. Now that TCP connections have been opened on "both sides", the mail client sends its message on that established TCP connection and the LTM forwards the data to the pool member. Once the entire message has been sent by the client, the client tears down the TCP connection and the LTM does the same with the pool member.

 

 

Because the entire message is sent on the same TCP session, no Persistence is required.

 

 

What it sounds like you are concerned about is how to load-balance when multiple SMTP messages are sent on the same TCP connection. But I suspect you don't need to worry about this, because I believe individual SMTP messages are sent on their own TCP connection.