Epidermal growth factor (EGF) binds to pancreatic acinar cells and facilitates recovery from acute pancreatitis (AP). In animal models, EGF protects against pancreatic injury and prevents septic complications. The role of EGF in human AP is unknown.The aim of this study was to assess EGF serum levels in AP patients and whether the EGF +61 G/A single nucleotide polymorphism (SNP) affects susceptibility and/or severity of AP.Hospitalized AP patients were prospectively enrolled. Demographics, clinical features, DNA and early serum samples were collected when available. Patients were classified into mild (79%) and severe AP (21%) based on organ failure for >or=48 h. Early serum samples were quantitatively assayed for EGF levels. The EGF +61 G/A SNP was evaluated by restriction fragment length polymorphism analysis.There were 179 patients ascertained with AP. EGF levels were measured in a subgroup of 60 patients with early serum samples (17 severe) and in serum from 58 healthy controls. Serum EGF levels within 48 h from the onset of pain were significantly lower in AP patients (mean 13.5 pg/ml) compared to controls (25.2 pg/ml; P=0.015). Furthermore, EGF levels were significantly lower in severe patients when compared to mild (7.8 vs. 14.3 pg/ml; P=0.026). DNA from all 179 patients and 189 healthy controls was sequenced. The EGF +61 G/A SNP did not affect susceptibility to or severity of AP.EGF serum levels are decreased early in the course of AP and are further suppressed in severe AP. The EGF +61 G/A polymorphism has no effect on AP.