My '68 has a 350 smallblock, 3 speed manual, and I guess 3.75 rear end, and I consistantly run it 70 -75 mph on the highway. My truck seems to like it but with a 4 barrel edelbrock it does drink a lot of go juice. 60 -65 mph is much friendlier though. I have also driven it 80+ mph and I felt like that was pushing it too much. My motor is a bone stock and on its 12th year on a rebuild.
I sometimes wonder how much longer will it last.