Lysosomal cathepsins D (CD), B (CB), and L (CL) serum levels were determined by immunoassays in patients with chronic (CHP) or acute (AP) pancreatitis and in patients with ductal pancreatic carcinoma (DPC) and correlated with some biological and clinical parameters of this tumor. CB serum concentrations significantly higher than those measured in healthy subjects (NS) were observed in CHP, AP, and DPC patients (p< 0.01). However, no significant difference was noted among these groups. Increased CL serum levels were evident only in cancer patients compared to NS, AP, or CHP groups (p< 0.05), while no difference was observed among these groups. Elevated CD serum values were observed in CHP and AP patients compared to healthy subjects or cancer patients (p< 0.01). In cancer patients no correlation between CD, CB, and CL and clinical stage or tumor size was found. However, significant correlations were observed only between serum CD and CA50 (p< 0.02) and between CD and CL (p< 0.05). No further relationship among the biochemical parameters examined was observed. The present data suggest that the different serum patterns of CD, CB, and CL in patients with pancreatitis and pancreatic cancer may be of clinical interest as additional biochemical parameters for the differential diagnosis of these diseases. However, further prospective clinical studies are needed to assess better their potential value as prognostic parameters to identify patients with pancreatitis at increased risk to develop pancreatic cancer.