In addition to its established function in the regulation of circadian rhythms, the "Drosophila" gene "period" ("per") also plays an important role in processing long-term memory (LTM). Here, we used courtship conditioning as a learning paradigm and revealed that (1) overexpression and knocking down of "per" in subsets of brain neurons enhance and suppress LTM, respectively, and (2) suppression of synaptic transmission during memory retrieval in the same neuronal subsets leads to defective LTM. Further analysis strongly suggests that the brain region critical for "per"-dependent LTM regulation is the fan-shaped body, which is involved in sleep-induced enhancement of courtship LTM.