Calprotectin (Cal) concentration is elevated in acute inflammatory reactions and its increase in the plasma suggests a diagnostic potential for Cal assay. This study aimed (a) to evaluate the Cal plasma levels in patients suffering from acute pancreatitis (AP) and (b) to assess whether early assay of Cal plasma levels can be helpful in assessment of the severity of AP. Forty-six consecutive patients, median age 45 years, suffering from a first attack of AP were recruited at two medical centers. Data collected on admission included age, sex, delay between pain onset and admission, and Glasgow score. A severe outcome was defined according to the Atlanta criteria. AP was defined as edematous or necrotic according to the CT findings. Plasma Cal and serum C reactive protein (CRP) were assayed in all patients within the first 24 hr after hospitalization. Sixty subjects suffering from blood hypertension were recruited as controls. Plasma Cal was measured by a commercial ELISA system. In all AP patients and in none of the controls, plasma Cal concentration was higher than the normal limit. Cal values in AP patients were significantly higher than in controls (P < 0.0001). There was not a statistically significant difference in Cal values between patients with severe and patients with mild AP. Plasma Cal values did not differ in necrotizing and edematous AP. During the follow-up plasma Cal was reassayed in six of the patients with abdominal fluid collection and the values were higher in the two patients with infected necrosis. We conclude that plasma Cal is elevated in patients with AP but it is not a useful marker for early prediction of pancreatitis severity. Further studies could evaluate its usefulness in pancreatic infected necrosis.