Bi-Polar?

The second week of owning my ball python went very well. He was calm and let me hold him without a hitch, not even a hiss of any sort. Now into the third week I can't open the cage door without him curling up, hissing and striking. He's about 4 months old, an 18" long. I was KINDA scared of snakes before i got him but now I'm too nervous to even try holding him...if I leave him alone for a day or two will the aggression go away?

It can come and go. I have a male orange ghost ball python who was sweet as a puppy when we first got him, and he's now nicknamed "satan", as he turned into an aggressive little turd in about a week. There is no need to be scared of him, you may have to take a few bites (which don't hurt, I promise). If you get bit while handling, don't put him away because then he'll realize when he bites, he gets what he wants. I suggest, if the husbandry is correct, handling in small increments. Maybe 5 minutes every other day, and working your way up in time. Don't give up, just tap him on the head with an empty paper towel roll before you reach in to pick him up.

If you're absolutely scared of handling because you think you might get bit, wear light gardening gloves that have mild roughness on them for extra grip and a long sleeve shirt. I did this with a wild caught watersnake who was very nippy. After awhile he figured out that biting wasn't going to do anything and he calmed down.

Also, you snake might be getting ready to go into the blue. My cornsnake is always more temperamental when she is heading that way.

Gardening gloves! Gardening gloves are the solution to (almost) all handling problems. Most especially handling problems that involve you and your snake being scared of one another.

(But it's very likely that he just went into shed. I have several animals that do the Dr. Jekyll/Mr. Hyde thing whenever they go into shed. Keep an eye on him for the next week. If his eyes turn cloudy and blue, then it's just a shed cycle. Dump out some water in the bedding or mist the tank daily to boost the humidity. He should cheer up again after he sheds.)