You're probably going to hate this answer, but the first step to publication is to write a book that someone wants to publish. If you've really sent hundreds of letters, then it may be time to either revise and polish your current manuscript or shelve it and write another book.
Once in a while, it's a matter of timing (i.e., having the right story at the right time for the right agent/publisher). Study the market as closely as possible and always be on the lookout for new, reputable agents. Read agent blogs and Web sites for clues as to what they seek.
There are lots of author stories online regarding the road to publishing. Some people weren't published for five years or more, or didn't get any bites until their ninth or tenth novel. So, sometimes we unpublished writers have to go back to the drawing board.
If you haven't had anyone critique your novels, or a sample of them, then I suggest you obtain some feedback just in case your writing needs some attention. Otherwise, keep your eye on the market and keep submitting if you can. It's a tough road, I feel your pain!
Good luck.