Specifically the difference between what the camera has focussed on and what your eye is trying to focus on.
When we look at things In Real Life we look at something close, like our hand, and objects in the background are blurred. Your eye is not focussed on them. If we look out to the middle distance though, our eye quickly re-focusses and things near to us become blurred.
But in a 3D movie this doesn't work. Whether something is in focus or not is decided by whether the CAMERA was focussed at that distance when it was filmed. This is just as true in 3D movies as it is in 2D movies.
Now in a 2D film your eye never changes focus. It's focus is the movie screen. There is the false focus of the camera, but we're used to that. It's one tool (the primary one) the director has for telling us what is significant in the current shot.
In a 3D movie however, apparent distance is changing and your eyes ARE adjusting shot by shot, for parallax at least. But you have to guess what the camera has focussed on, or your eyes are going to strain to focus on objects that will simply never come into focus.
This is why 3D movies are so much more tiring to watch. And one of the reasons why it's not real 3D. And why I'm still suspicious of whether it will ever become the dominant form in the art of cinema.
Interestingly, there is the potential for CGI to make much better 3D movies, for the simple reason that everything can be in focus all the time. I have yet to see a fully CGI movie in 3D I believe.