Spatial familiarization consists of a decrease in the exploratory activity over time after exposure to a place. Here, we show that a 30-min exposure to an open field led to a pronounced decrease in the exploratory behavior of rats, generating context familiarity. This behavioral output is associated with a selective decrease in hippocampal PKM[zeta] levels. A short 5-min exposure did not induce spatial familiarity or a decrease in PKM[zeta], while inactivation of hippocampal PKM[zeta] by the specific inhibitor ZIP was sufficient to induce spatial familiarity, suggesting that the decrease in PKM[zeta] is involved in setting a given context as a familiar place.