OK, this begins to drive me crazy. I have an asp.net webapp. Pretty straightforward, most of the code in the .aspx.vb, and a few classes in App_Code.
The problem, wh
Sounds like it happens every time the website spins up (the app gets recycled every time you touch app_code and probably you have IIS configured to shut down the website after X minutes of inactivity).
I bet it has something to do with the asp.net worker process not having the correct access rights on the server. So its trying to load an assembly and is being denied.
Check this link and Table 19.3 for a list of all the folders the worker process account must have access to in order to function. And don't forget to give it rights to all files and folders in your virtual directory!