The memetics movement split almost immediately into two. The first group were those who wanted to stick to Dawkins' definition of a meme as "a unit of cultural transmission". Gibran Burchett, another memeticist responsible for helping to research and co-coin the term memetic engineering, along with Leveious Rolando and Larry Lottman, has stated that a meme can be defined, more precisely, as "a unit of cultural information that can be copied, located in the brain". This thinking is more in line with Dawkins' second definition of the meme in his book The Extended Phenotype. The second group wants to redefine memes as observable cultural artifacts and behaviors. However, in contrast to those two positions, Blackmore does not reject either concept of external or internal memes.[11]

These two schools became known as the "internalists" and the "externalists." Prominent internalists included both Lynch and Brodie; the most vocal externalists included Derek Gatherer, a geneticist from Liverpool John Moores University, and William Benzon, a writer on cultural evolution and music. The main rationale for externalism was that internal brain entities are not observable, and memetics cannot advance as a science, especially a quantitative science, unless it moves its emphasis onto the directly quantifiable aspects of culture. Internalists countered with various arguments: that brain states will eventually be directly observable with advanced technology, that most cultural anthropologists agree that culture is about beliefs and not artifacts, or that artifacts cannot be replicators in the same sense as mental entities (or DNA) are replicators. The debate became so heated that a 1998 Symposium on Memetics, organised as part of the 15th International Conference on Cybernetics, passed a motion calling for an end to definitional debates. McNamara demonstrated in 2011 that functional connectivity profiling using neuroimaging tools enables the observation of the processing of internal memes, "i-memes", in response to external "e-memes".[12]

An advanced statement of the internalist school came in 2002 with the publication of The Electric Meme, by Robert Aunger, an anthropologist from the University of Cambridge. Aunger also organised a conference in Cambridge in 1999, at which prominent sociologists and anthropologists were able to give their assessment of the progress made in memetics to that date. This resulted in the publication of Darwinizing Culture: The Status of Memetics as a Science, edited by Aunger and with a foreword by Dennett, in 2010.