Hungry medicinal leeches, Hirudo medicinalis, bite warm surfaces and ingest blood meals averaging 890% of their weight. Satiation lasts 12-18 months during which leeches avoid warm surfaces and will not bite. The segmental nervous system of the leech is distinguished by a population of neurons which contain serotonin (5-Hydroxytryptamine, 5-HT) at high concentrations. Some of these identified 5-HT neurons directly activate the effectors responsible for three physiological components of feeding: salivary secretion, bite-like movements and pharyngeal peristalsis. A localized warming of the lip is sufficient to initiate ingestion and synaptically excites anterior 5-HT cells into high frequency impulses or bursts. Distension of the body wall terminates ingestion and also hyperpolarizes these 5-HT neurons. Serotonin treatment produces hyperphagic behavior by the leech, while a specific pharmacological lesion of its 5-HT cell produces the anorexic behavior of satiation. This anorexia is transiently reversed by 5-HT treatment. Serotonin plays an obligatory role in the initiation and expression of leech feeding behavior by its differential modulation of central neuronal networks and peripheral glands and muscles.