The medial temporal lobe is crucial for the ability to learn and retain new declarative memories. This form of memory includes the ability to quickly establish novel associations between unrelated items. To better understand the patterns of neural activity during associative memory formation, we recorded the activity of hippocampal neurons of macaque monkeys as they learned new associations. Hippocampal neurons signaled learning by changing their stimulus-selective response properties. This change in the pattern of selective neural activity occurred before, at the same time as, or after learning, which suggests that these neurons are involved in the initial formation of new associative memories.