This particular decree of the British is often blamed for being a contributing factor to the American Revolution, but it did have importance in keeping conflict with American Indians down. So what might happen if Britain had effectively declared open season on the trans-Appalachian lands for any Americans to seize at their will?
There were plenty of Americans in the trans-Appalachian districts OTL (Watauga in Tennessee, for instance), so what if these settlements and such were legal and thus protected by the British? How might this affect the American Revolution as well as settlement of trans-Appalachia? Could there be a 14th colony (or more) organised from trans-Appalachian lands, or will the 13 colonies hold onto their land claims as they did post-Revolution? And if the American Revolution is delayed long enough, the people there will be pressing for control over the Mississippi, since that river is absolutely critical for the economy of the trans-Appalachian lands to function.