A lot of hot rodders have pickup trucks as daily drivers and parts haulers, but as evidenced by the number of tailgate-less pickups I see running around the freeways of SoCal the tailgate myth perpetuates... Simply stated, putting your tailgate down- or worse yet removing it- will not help your fuel mileage. In fact the opposite is true; in most cases it will negatively impact it.
Why? Lowering the tailgate actually increases drag and lift at the rear of the truck which can noticeably affect efficiency and mileage. Removing it only increases the negative effects by shortening the surface area, and net style tailgate replacements create the most drag of all. There's a lot of aerodynamic theory at work here, but the simplified explanation is this; while driving the air within the bed literally rolls into a vortex (somewhat observable by noting the erratic flight of paper or leaves in the bed while driving) and creates a cushion of air referred to as a separation bubble. Airflow coming across the cab sees this bubble as part of the truck and as such it flows more smoothly over the bed, in turn creating less suction (aerodynamic drag) at the rear of the cab and bed. Note in the photo from Ford's aerodynamic testing of the '09 F150 at a simulated 80mph that the smoke from the wand does disperse as it flows past the cab, but still maintains an arc that flows toward the tailgate. With the tailgate down, removed, or replaced by a net, this bubble does not form and airflow from across the cab flows down into the bed greatly increasing suction against the back of the cab. So what's the fix? A hard tonneau cover is an excellent option that positively affects airflow, as is an aero style camper shell. However, for the ultimate airflow improvement, a cover that creates a wedge shape that flows from the back of the cab to the tailgate, like this one, would be ideal aerodynamically speaking- though perhaps not aesthetically. On a side note; on most trucks, especially older ones, the tailgate is actually a structural member of the bed. Leaving it off or down can over time actually result in weakening of the attachment points of the bed sides due to vibration and flex.