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Just disabling cylinders might get you 10-15% depending on the application and how it's driven. To get the most out of it, you would have to eliminate the drag of the dead cylinders by removing rods, pistons, valve trail components. Ford had a 300-6 that would disable half of the valves to make a 3 and it had some increased mpg, but nothing crazy because the pistons were still in there.
The 300-6 will run smoothly with the front/rear 3 cylinders only
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1991 F-250:
4.9L, Mazda 5 speed, 4.10 10.25" rear
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