You may get this the first time you try to execute an ASP.NET site on a Windows XP installation of IIS 5.1 The error will point you to a Microsoft Knowledge Base article to solve the Failed to Access IIS Metabase error that instructs you to use a Metaacl.vbs script to apply permissions to the IIS Metabase on your workstation. This is fine for older versions of ASP.NET, but with ASP.NET 2.0 and above you need to be aware of the aspnet_regiis command line utility.
The aspnet_regiis utility is located in the %Windows%\Microsoft.NET\Framework\v2.0.50727 folder on your system. So you will need to bring up a command prompt and change to the folder or have it in your system paths.
Once you can execute the aspnet_regiis, add the -i or the -ir command switch to install or reinstall ASP.NET on your system. The first switch will install and upgrade all application pools in the existing instance of IIS, which may not be exactly what you want to do. The second option just installs ASP.NET 2.0, but may not necessarily solve the issue.
What has most likely happened to cause the error is the required permissions have been removed from the web site's folders. If you are in a corporate environment this can happen if your network monitors access permissions, services, etc and forces them back to a standard state. I have seen this be a problem with systems I was working on at various client sites over the years, not just with this issue, but many other applications and utilities we were using, so be aware of your infrastructure.