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The obese gene product, leptin is an important circulating satiety factor that regulates energy balance via its actions in the hypothalamus. However, leptin receptors are also expressed in brain regions not directly associated with energy homeostasis, such as the hippocampus. Here, leptin inhibits hippocampal neurones via activation of large conductance Ca²⁺‐activated K⁺ (BK) channels, a process that may be important in regulating neuronal excitability. We now show that leptin receptor labelling is expressed on somata, dendrites and axons, and is also concentrated at synapses in hippocampal cultures. In functional studies, leptin potently and reversibly reduces epileptiform‐like activity evoked in lean, but not leptin‐resistant Zucker fa/fa rats. Furthermore, leptin also depresses enhanced Ca²⁺ levels evoked following Mg²⁺ removal in hippocampal cultures. The ability of leptin to modulate this activity requires …