Abstract The effects of lithium treatment on serotonin (5-HT) binding sites in the rat brain were investigated. Oral administration of lithium carbonate for 3 weeks did not influence 5-HT 2 binding sites in the cerebral cortex. On the other hand, the number of 5-HT 1 binding sites labeled with [ 3H]5-HT was decreased significantly in the hippocampus, but not in the cerebral cortex. While non-5-HT 1A sites, defined as specific [ 3H]5-HT binding in the presence of 100 nM 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT), were not affected by lithium treatment in either brain region, chronic lithium administration reduced significantly the density of 5-HT 1A sites labeled with [ 3H]8-OH-DPAT only in the hippocampus, but not in the cerebral cortex. These results suggest that 5-HT 1A components are responsible for lithium-induced down-regulation of 5-HT 1 binding sites in the hippocampus and that 5-HT 1A sites in the hippocampus might be connected with the therapeutic efficacy of lithium.