The adult human cerebellum expresses melatonin receptors with high density in the external zone of the molecular layer. Cloning of the receptor cDNA isolated by RT-PCR from human cerebellar specimens and sequencing analysis of the full-length coding region revealed that the receptor protein is encoded by a transcript identical to that recently cloned from the human hypothalamus (Mel1a). In situ hybridization using an antisense cRNA-probe demonstrated that the melatonin receptor mRNA is localized in the cerebellar granule cells. Mapping of the messenger by RT-PCR with Mel1a specific primers in different areas of the human brain disclosed a quite widespread distribution of the transcript, although expressed at very low levels. Semi-quantitative comparison between the different brain regions allowed to establish the following relative mRNA abundance: cerebellum > or = occipital cortex > or = parietal cortex > temporal cortex > thalamus > frontal cortex > or = hippocampus. No mRNA was detected in white blood cells.