We've had a Win2003 server running PHP 5.1.4 with IIS 6 and MySQL for over a year.
A few days ago all sites relying on PHP just stopped coming up and indicate 404 file not found. We can't even get our check file with phpinfo() to work.
We were using PHP-cgi but switched to PHPisapi.dll after some research.
After making the switch all sites began working again for about 3 days and now they've stopped with the same 404 error.
No changes were made to any sites prior to PHP just not working and all files, extensions and script mappings are as they should be.
have you tried hitting a plain HTML file in the same location as the PHP? If yes and it comes up, I'd remove the extension mappings in IIS and recreate them. Also make sure you have the appropriate .dll files in the environment path.