Final answer:
The main issue that the Federalists and Anti-Federalists disagreed on was the power of the national government. Federalists believed in a strong central government, while Anti-Federalists were concerned about the power of the national government and favored state legislatures.
Step-by-step explanation:
The main issue that the Federalists and Anti-Federalists disagreed on was the power of the national government. Federalists believed in a strong central government and supported the ratification of the Constitution. They believed that a strong government would be better for national defense and economic growth. On the other hand, Anti-Federalists were concerned about the power of the national government and believed that state legislatures could better protect individual freedoms.