I seem to remember issues with the ashx handler not being picked up when aspx files resided in subfolders in IIS6. Is this the case?
I've been just playing with the configurable solution which allows the handler be configured in the web.config instead of as a .ashx file, does this solve the issue? if there is one! A simple test worked perfectly for me, a once off configuration covered the whole application, eliminating the requirement for the same .ashx in all of my clients aspx directories.