The primary cause of the American Civil War was the issue of slavery.
The war was fought between the Northern states (the Union) and the Southern states (the Confederacy), primarily over the issue of whether slavery should be allowed in the new states joining the Union. The Southern states depended on slavery for their economy, while the Northern states wanted to abolish it. The disagreement over slavery became the key issue leading to the Civil War.
Hence, the correct answer is The issue of slavery.