The federalists and anti-federalists argued primarily over which issue?

They argued primarily over the strength of the national government in the newly formed United States.

They argued over many things, but mainly:
-How to interpret the Constitution
-How to go about international diplomacy with France and Britain while they were at war
-The creation of a national bank
-How to handle state debts (let them deal with it or let the national government take it on)
-Tariffs and taxes on the citizens and foreign goods