I've been having issues recently that seem to have a common thread - problems with paths to various files in my install. Most of these issues erupted when I upgraded to 2.8.1 and changed my .htaccess file to add "AddHandler application/x-httpd-php5 .php" as the very top line. Apparently the default install at Psek (an Incsub partner) is PHP 4. I read a post on these forums that suggested making this particular change to .htaccess in order to ensure I was running under PHP 5. Aside from that, the .htaccess file is whatever the default WPMU install is.

The most recent path related problem involves a couple of plugins that add buttons to the TinyMCE editor which display "pop-up" windows for editing - in particular the cforms II plugin. When I click the button to add a form, I get a themed 404 in the pop-up. This is also happening with another plugin that is used to add video to a post.

If I type the URL to any PHP in the Plugins folder directly in a browser (e.g., http://mydomain.com/wp-content/plugins/cforms/abspath.php OR http://mydomain.com/wp-content/plugins/test.php ), I get the 404 as well. I tried putting a simple image file into the plugin folders (e.g., wp-content/plugins/cforms/test.jpg) and was able to access that directly via the browser. I was also able to access an HTML file (e.g., http://mydomain.com/wp-content/plugins/cforms/abspath.php) as well as a .txt file. However, any PHP file in the Plugins folder I try to access directly throws a 404. I tried setting permissions for the folder and all files to 755 and even 777 to see if it was a permissions issue - still the 404.
FWIW, I noticed that this inability to directly access PHP files within the wp-content directory is not exclusive to the Plugins folder - the issue happens with ANY PHP file within the wp-contents directory - no matter where in the tree it happens to be.

I have another WPMU install on a different server - PHP 5 running WPMU 2.8.1 - where this problem is not happening. And I can directly access any PHP files in the wp-content directory without a 404.

My suspicion is that something may be screwy with my .htaccess file. Ideas? Below is my .htaccess file:

AddHandler application/x-httpd-php5 .php

RewriteEngine On
RewriteBase /

#uploaded files
RewriteRule ^(.*/)?files/$ index.php [L]
RewriteCond %{REQUEST_URI} !.*wp-content/plugins.*
RewriteRule ^(.*/)?files/(.*) wp-content/blogs.php?file=$2 [L]
RewriteRule ^(.*/)?avatar/(.*) wp-content/avatar.php?file=$2 [L]
RewriteRule ^(.*/)?sitemap.xml wp-content/sitemap.php [L]

# add a trailing slash to /wp-admin
RewriteCond %{REQUEST_URI} ^.*/wp-admin$
RewriteRule ^(.+)$ $1/ [R=301,L]

RewriteCond %{REQUEST_FILENAME} -f [OR]
RewriteCond %{REQUEST_FILENAME} -d
RewriteRule . - [L]
RewriteRule ^([_0-9a-zA-Z-]+/)?(wp-.*) $2 [L]
RewriteRule ^([_0-9a-zA-Z-]+/)?(.*\.php)$ $2 [L]
RewriteRule . index.php [L]

<IfModule mod_security.c>
<Files async-upload.php>
SecFilterEngine Off
SecFilterScanPOST Off
</Files>
</IfModule>