I recently adapted my .Rprofile and was puzzled when RGui did not load the new .Rprofile (RStudio did load it) but instead held on to the old version. After some trial and error I figured out that the .RData-file in the working directory was the reason for that and after deleting it RGui was using the new .Rprofile.
I was wondering why this happens as I was not aware that .RData does save a copy of .Rprofile that dominated the new .Rprofile stored in the working directory. ?Startup suggests that R first searches for .Rprofile and then loads the user workspace from .RData.