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It is stated in the Animatrix short World Record that only exceptional humans tend to become aware of the Matrix, those who have "a rare degree of intuition, sensitivity, and a questioning nature", all qualities which are used to identify inconsistencies in the Matrix. The narrator then adds that "some attain this wisdom through wholly different means".
Self-substantiation is never thoroughly discussed in any part of the series, although people who have achieved it are mentioned:
- In The Matrix, Morpheus speaks of the founder of Zion, saying that he freed himself. This is presumably an instance of self-substantiation, but this story is unlikely to be true.
- The Kid puts his faith in Neo and commits suicide, removing himself from the Matrix in Kid's Story.
- Dan Davis manages to temporarily exit the Matrix without the use of a Red Pill in World Record.
- The protagonist of the short story "Goliath" starts to realize that the Matrix isn't real as he sees everything melt into a puddle when Aliens destroy the central processing unit he is connected to. His girlfriend leaves after he tells her "about how we were really just hanging there, plugged and wired, central processing units or just cheap memory chips for some computer the size of the world, being fed a consensual hallucination to keep us happy, to allow us to communicate and dream using the tiny fraction of our brains that they weren't using to crunch numbers and store information."
- In "Sweating the Small Stuff", Dez thinks at first that he's losing touch with reality, feeling he can't trust reality any more and seeing through it to the numbers in the matrix code, once per. He ends up on the run from Agents with his girlfriend Mia trying to find answers.
- The Stockbroker's wife in "Déjà Vu" awakens to the real world during nightmares, seeing both realities concurrently.
- Emma Pearson in "A Path Among Stones" believes that nothing she sees is real, and she can see reality when closing her eyes. She stuck wires into her doll, saying that is how he is when she closes her eyes and is scared when underwater, saying she can't breath and can't remember how to get out. This all leads to her being examined by psychiatrists, being diagnosed as schizophrenic and finally taken away by Agents.
- Raven Underwell in "Artistic Freedom" was inspired to create statues of various Machines after a "startlingly vivid dream", in reality waking from the Matrix to see the pod she was in, the power plant she was part of and the Docbots and Sentinels maintaining them.
- Jeffrey Zeiss, an E Pluribus Neo liaison in The Matrix Online self-substantiated after a heart attack, escaping the Matrix and picked up by a hovercraft looking for a redpill they had just freed.