AIM: Serotonin is a one of the monoamine neurotransmitters secreted by serotonergic nerve endings in multiple sites in the brain and gastrointestinal tract wall. Serotonin can induce contraction in the smooth muscles of the gut wall enhancing gut motility and in blood vessels wall causing vasoconstriction. The presence of serotonin receptors on hepatic stellate cells can cause contraction of these cells closing the sinusoidal fenestrae and raising the portal vein pressure. The aim of this work is to study the relation between serotonin level and the presence and the severity of esophageal varices in Egyptian patients with viral hepatitis related cirrhosis. PATIENTS AND METHODS: Two hundred patients were included in the study group I: 120 patients with viral hepatitis related cirrhosis and group II: 90 healthy volunteers. Patients as well as healthy subjects performed all routine investigations, upper GI endoscopy and serum serotonin level. RESULTS: serum serotonin level in group I was significantly higher than group II (135 ± 33.7 vs 41 ± 19.6). serum serotonin level was significantly correlated to albumin, bilirubin, platelet, portal vein diameter, spleen size, esophageal varices grade, grade of portal hypertensive gastropathy and Child's score (r = -0.35, 0.45, -0.44, 0.5, 0.39, 0.33, 0.36 and 0.41 in succession). It was also clear that serotonin level rises significantly with higher grades of esophageal varices. CONCLUSION: serum serotonin level is significantly correlated to the grade of esophageal varices in patients with viral hepatitis related cirrhosis.