When 8 year old Mac's mother tells him that he's too old for an imaginary friend, he brings Blooregard "Bloo" Q. Kazoo to Foster's Home For Imaginary Friends where he is told that Bloo won't be adopted if Mac visits him every day. Soon after, Mac's older brother Terrence and an evil imaginary friend named Duchess make a plan to try to get rid of Bloo. Mac, with the help of friends named Wilt, Eduardo, and Coco, try to stop them.

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Mr. Herriman sends Frankie to the mall to get streamers for Madame Foster's birthday party, and Mac, Bloo, Eduardo, Wilt, and Coco end up coming along. Eventually, they each wander off in a different direction after being distracted by something.

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Bloo discovers a door in Foster's that everyone is forbidden to open, and nobody tells him what's behind it. One night he opens it, and releases Scribbles, a friend that does jobs around the house and causes everyone to become lazy.

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After Bloo accidentally breaks a statue of Madame Foster, he and the other friends try to hide it from Mr. Herriman.

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Bloo shows something to Mac from the roof of Foster's, and then neither can find their way downstairs for dinner. Mr. Herriman insists that no one can eat until Mac and Bloo arrive, and Madame Foster helps sneak them food while Herriman isn't looking.

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Mr. Herrmian is filmed dancing embarrassingly by Mac and Bloo, and the video eventually ends up on the Internet which causes Herriman to be humiliated.

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A new friend named Berry arrives at Foster's, and seems nice to everyone. Soon, she starts to try to kill Mac because she thinks that Mac is getting in the way of her being with Bloo, who she loves. Meanwhile, Bloo barely even realizes she's there.

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Terrence creates a friend named Red to beat up Mac and Bloo; Bloo tries to get the same praise that Wilt does for rescuing imaginary friends, so he brings a man in a cell phone costume to Foster's.

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Eduardo tries to hide a puppy he found from Mr. Herriman, who has a fear of dogs and doesn't let them in Foster's.

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Mac and Bloo try to force the friends back in the house on Adopt-A-Thought Saturday so that they won't be adopted.

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Mac and Bloo get sick after playing in the rain, causing them to miss watching a scary movie with the other friends. Wilt, Eduardo, and Coco mistake Bloo for a ghost, and Frankie gets locked out of the house in the rain.

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