If you have a carburator, you can probably jet it to deliver the proper mixture of E85. Electronic fuel injection may be able to be fooled. CIS would pose problems. But in all of these cases, you would the be forced to always use E85 unless you undid the changes.

A friend has a Ford 460 with a (big) carburator, and when E85 is finally more available here, I would like to tune it to run on the stuff. His milage is already total crap, but I think we could squeeze a few more HP out of the engine just by running E85, at the cost of a further loss of milage.