My dad used to have a late 70's C10 with the 250, he said that it got crappy gas mileage, even worse than some of the V8 cars hes had. Those inlines have a really low comp ratio, which may be why. Probably if you built one to run higher comp and a few other doodads, you could get better mileage.
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1969 GMC K2500 
1996 Honda Accord
2007 Kawasaki KLR 650
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