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My iMac has 4 memory slots - it came with 2 standard at 2GB each. I am thinking of adding more RAM so I want to figure out if it’s going to work if I just add 1x4GB and leave one slot empty in case I’d like to add more RAM or I have to fill both free slots with 2GBs? Thanks in advance.

Fill it up with whatever you can afford. Big chips are bigly money, as Trump might say ;) Apple recommended guidelines max out at 4 x 4 GB in each slot for a maximum of 16 GB of memory for your machine specification. However, third-parties have discovered that it actually will support 32 GB of memory using 4 x 8 GB modules. This might shorten the lifespan of your board though. Boo! You probably know: If not, This is the guide page how to do it. iMac Intel 21.5" EMC 2428 RAM Replacement If you can get your RAM off ifixit, return the favour: PC3-10600 4 GB RAM Chip PC3-10600 8 GB RAM Chip

You really need to use two DIMM’s but they don’t need to be 2 GB modules. You can mix different pairs to the max of 16 GB.