You can begin submitting letters to AMCAS as soon as the application opens in May. Before you mail a letter to AMCAS, you must create an entry for that letter in your AMCAS application. To create an entry, you will have to tell AMCAS who the letter writer is and name that letter. AMCAS will then give the letter an ID number. When you send your letters, the letters must have both your AMCAS ID number and letter ID number. If you are using a letter service from your school or Interfolio, there are special instructions you must follow since you do not have access to go and modify those previously stored letters. Be sure you know how your letter service works before sending letters to AMCAS through the service.
One important thing to know is that you can create and submit letters any time during your primary application. This includes before you submit, after you submit, and after your application is verified. This is one of the few parts of the application that you can actually edit after submission.