As I said over in the gas prices thread.... I run E85 in my 2011 Suburban whenever I can. The biggest issue here is that there are only four stations in the entire state of Oregon that sell it. If I have to tow anything south though, it is a huge money saver to be able to run E85 and the truck REALLY likes it, especially in hot weather or towing. Running an ethanol blend on a modern engine with proper tuning up to ~40% ethanol will actually get you an overall INCREASE in fuel mileage due to you being able to run leaner fuel mixtures and better ignition timing, but most engines are not properly tuned or set up for that. When I blend E85 with E10 pump gas to get ~30-40% content I have seen an increase in mileage. Once you have full E85 in there at 60-85% ethanol content the mileage does drop quite a bit. I made a trip down to Southern California a few weeks ago pulling an enclosed car trailer and I got ~10-12mpg while towing. The 6.2 is running ~10.5:1 compression so it likes to have at least mid-grade in it when towing. In oregon, mid grade was ~$4.89/gal and E85 was $3.99/gal. Redding, CA had mid-grade at $6.29/gal and E85 at $3.49/gal. All stations south of Sacramento had Mid-grade ~$6.49/gal and E85 at $2.99/gal. Obviously it was highly beneficial to have higher octane than premium at less than half the cost. I ended up spending about half the amount on fuel for the round trip as my BIL, who has a 2023 Ram Rebel and towed the enclosed trailer down empty and towed a fairly light jet boat back up. I was pulling the enclosed trailer with a complete C10 chassis including a 454/TH400 and a bunch of spare parts in it... just missing the cab and bed.
I can probably run E85 in my 1980 K25 with the newer engine in it, but I would need to install a flex fuel sensor and convert the P01 computer to a P59 computer running a flex fuel OS. It's really only possible because I have the 24x reluctor on the 454, individual coil packs, and larger injectors than needed. Unfortunately it would probably require me to convert to DBW as well.