Many years ago in a college physics class we did a project where we analyzed this. We actually constructed balsa wood pickup bodies and attached identical wings to them and tried to make them fly. The pickup body with the tail gate down required considerably more flap to keep the nose attitude down and flew quite a bit shorter distance when launched from the same catapult in the gym as the pickup body with the tailgate up. The tailgate up body had less drag and flew a further distance each time. We consulted an guy with a doctorate in aeronautic engineering about our conclusion. He did mention that we developed a detached vortex with the tailgate up and, that resulted in less drag on the body.
So, I was pleased that the Myth Busters came to the correct conclusion. However, I do have to discount their "identical" truck experiment some because no two trucks are actually identical. There could well have been enough variation in the trucks to allow one to travel 30 miles further on a tank of fuel than the other. That is besides the fact that individual driving habits could also result in as much of a variation. No matter, their "test" resulted in the correct outcome. Their water flow test with oatmeal was more accurate since the only difference was the tailgate on the same body with the same flow.
Interesting enough, in college, nobody in the class thought that their model with the tailgate up would have less drag. We tried hard to make the tailgate down model fly better to prove our hypothesis correct. It just wasn't happening.
