This mission will not begin until you have collected all 50 Letter Scraps, which are available from the beginning of the game, but note that the mission can only be completed by Franklin. Once you have gotten all of them, a question mark will appear in the Vinewood Hills section of Los Santos. It's ideal to flatten all of the tired of the vehicle in front of the house.
When you arrive, you see Dreyfuss meditating and after some conversation, he will begin to run. If you shot the tires of the vehicle out front, he will run away on foot; otherwise, he will get in the vehicle and you'll have to give chase. You can let him get away if you want, but it might be more fun to kill him. Whichever method you choose, the mission will end.