I'm playing a new challenge neighbourhood that I'd like to use various hacks on - 'ACR', 'Edukashun iz gud', 'no20khandouts' etc. However I only want these for my challenge hood. Can I have them in a folder that I take in and out of Downloads depending on whether I'm playing that neighbourhood or not? I'm worried that taking it in and out will lead to corruption, especially ACR.

What I do is to have a whole folder for each hood that uses different CC. Then I just rename them according to which game I want to play- the one you name The Sims 2 (or Sims 2 ultimate depending on your game) is the one that is used by the game. That way makes it easy to have lots of different game configurations.

OK, thanks, that sounds like a good solution! Doesn't it take forever to load though, re-establishing all your CC? I'd also like custom careers in my challenge hood. Is that safe, if I move the whole Sims 2 folder?

For the custom careers, make sure that NO one is in them BEFORE they get taken out. That's really the only thing you need to remember when taking out mods.
Normally, I don't really have my game load slower than it already is when I'm re-moving CC in or out. If you move CC in in small portions then it will have better loading times if it doesn't already do.

So is that the case even if I'm moving out the whole folder, and not playing the challenge hood again until it's replaced? Say I have Emily, in my 'challenge' Legacy hood, in a hairdressing career. If I exit the game, move out the whole Sims 2 folder, replace with my 'everyday' sims folder, play til bored, exit the game and reinstate my Legacy hood folder, is Emily still there perfectly happy in her hairdressing career or have I screwed everything up?

As long as you keep the career that she is put in the game folder, you should be all right-you have to make sure you keep it in there.

As others have said, you should keep the CC you want to use in the same folder your "themed' game is in-like for me, I have a medieval hood, complete with custom careers, mods, clothes and other things-they all stay together in the same folder.

When I want to play the Medieval game, I rename the standard game "Sims 2 Modern" and then delete the name "Medieval" from the medieval one that I want to play. The game automatically loads that one.

The folder has to say, "Sims 2" only no matter what the theme in order to play the game at all.

The only folder I really copy between themed games are my mods-they, for the most part, stay the same and don't change in either game.

It depends on how you do it. Most stuff is safe to remove. Anything that isn't safe is usually fine if you remember to put it back in before loading that hood again. When there are files I want in some hoods but not others (like zombieapoc), I put them in a subfolder that I pop in and out of my Downloads folder. then again, I don't have a ton of mods/hacks that are hood-specific (like how some people have different default replacements for different hoods) so it doesn't take me long at all.

Some hacks are safe to move in and out.

However, a lot of hacks have tokens. ACR, Cyjon's Loan Jar, Monique's banking system, plenty of others that I don't feel like listing off the top of my head. If you pull them, the game will delete the tokens upon loading to neighbourhood and you'll lose settings.

You also don't want to pull custom memories, careers (unless you're absolutely sure it's unused), foods, or NPCs. Though for NPCs, you can copy the character files to the Characters folder.

This is only if you actually load the hoods where you've used them, right? Not if you load the game in general?

I'm not actually sure.

Yes, it is.

I believe memories are removed on loading the neighborhood. You can check when the invalid plantman counted token disappears.

If you remove a large number of important hacks, and then load a lot with them absent, it may get reset, causing people to be rudely interrupted from their actions. This is not good if they are off-world at work or similar activities.

I just want to add some information to @jonasn 's post: Important hacks as in global mods which affect everything. For example, a career isn't a global mod (Correct me if I'm wrong).
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People usually say to keep memories if you've used them. Tokens need to be deleted before you remove a hack.

Why do they say that tokens need to be deleted by hand? They are automatically deleted if the mod that contains them is removed.

I tried to make an invalid token deleter, but found that it didn't have any work to do.

I was just going by this, but it's possible that the information is limited to just the tokens in this hack. http://www.cyjon.net/node/68

Warning: If you ever want to uninstall this mod you must use Cyjon's Debugger to destroy the tokens first or risk corrupting your neighborhood. Instructions are included in the zip file.