Interstate 81 is a southwest to northeast Interstate in the eastern US. Starting at a junction with Interstate 40 near Dandridge, Tennessee, it continues 855 miles or so to Wellesley Island at the Canadian border in New York. The only metropolitan areas that Interstate 81 connects are Harrisburg, Pennsylvania and Syracuse, New York.
Interstate 81 is the longest north-south Interstate that doesn’t end in a 5 and is the 3rd longest that doesn’t end in 0 or 5. I-81 largely follows old game trails along the Appalachian Mountains and former Civil War trails. It is part of the fastest route from the capitol of the US to the Capitol of Canada.