Valid Sender
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Have you ever wondered what would happen if you replied to spam and asked them to remove you from their list? If they aren't a reputable company (which many aren't) you will be flagged as a "live prospect" and your name will probably be sold to other spammers. By replying, you let them know that there is a real person at an active e-mail account. You may not be able to e-mail them back for a number of reasons. The Valid Sender Analyzer looks for these reasons and increases the spam points if the e-mail fails the tests. If the "From" address is not the same as the "Reply To" address, it may indicate deception and some points will be added. The addresses not matching often occurs when a company hires a spam company. The "Reply To" goes back to the spam company so they can handle the backlash. The Valid Sender Analyzer also looks for an empty "From" address. If there isn't anybody to whom you can send a reply, it isn't likely that the e-mail is good. The final steps are to verify that there is an IP address to which a reply could be sent. If that works, then a quick test lets the Valid Sender Analyzer know whether there is a real computer receiving e-mail on the other end.  

The Valid Sender Analyzer looks at the sender of the e-mail to determine their willingness to accept a return e-mail. Usually spammers don't want to be contacted. They send out millions of e-mails and if even 1% replied to ask a question, it would be very bad for them.

The first test is whether the From is equal to the Reply To address. E-mails can have one address that specifies where it is from (often a lie), and another address for where a reply should go. If the two don't match it is a indication of spam. Sometimes a company (not very reputable) will contract with another company to handle the spam responses. In this case From might be
while the Reply To could be

The second test is whether there is a real e-mail address to which you could send a reply. The spammer might send no From address at all. If the From is blank, it probably means they don't want to be contacted and the probability is high that the message is spam.

An MX Record test takes a few seconds. Your computer will look up the e-mail address and make sure there is an IP address available to send a reply if you wanted to send one. In the physical world this would be equivalent of looking up the return address on an envelope in the phone book.

If the MX Record succeeds then we can do one more test - the SMTP test. The SMTP test takes some time. We can check to see if there is a server there to accept our reply. In the physical world, this is equivalent of driving to the return address listed on the envelope and making sure there is a mailbox there.

You may not want to do an MX record check and SMTP test on every e-mail. Put those domains in the box. There are two good reasons not to do the test.
1)Some domains don't allow an SMTP test without first sending e-mail. These would fail the SMTP test every time.  
2)Your business domain. There is no reason to check your own domain every time. At a company you would get lots of e-mail from that one domain.