Whether hyperlipidemia is a pre-existing metabolic disorder or a consequence of acute pancreatitis is still debated. Mild to moderate elevation of serum triglyceride levels are likely to be an epiphenomenon of the pancreatic disease. A marked hyperchylomicronemia and hypertrygliceridemia would be needed to trigger acute pancreatitis; a relevant defect in the lipid catabolism and clearance should therefore pre-exist. The aim of the present study was to investigate whether patients with acute pancreatitis and marked hyperlipidemia have an impaired clearance capacity of exogenous lipids, which would define the hyperlipidemia as a preexistent abnormality and therefore a potential cause of the pancreatic disease. With this aim, the kinetics of the removal of exogenous triglycerides from the circulation have been analyzed. Twenty patients with acute pancreatitis have been studied. Ten of them suffered from an episode of acute pancreatitis with marked hyperlipidemia (serum triglyceride levels > 20 mmol/L). Four to six months after recovery from the pancreatitis, a two-stage infusion of Intralipid 20% was carried out and the fractional removal rate (K2) and the maximal clearance capacity (K1) of exogenous triglycerides were calculated. At low infusion rates a first order kinetics for removal was observed, whereas at high infusion rates a zero order kinetics was operating. All patients with a previous attack of normolipidemic acute pancreatitis had normal K2 and K1 values. Five patients with previous hyperlipidemic acute pancreatitis had an abnormally low clearance capacity of exogenous triglycerides, whereas the remaining five had normal removal values. The present study provides new information in the association between hyperlipidemia and acute pancreatitis by showing that even a marked elevation of serum lipid levels should not be invariably considered as the etiological factor of the pancreatic disease, even if other potential causes are not evident.