We observed a putative immunocytolytic factor secreted in the supernatant of several pancreatic adenocarcinoma cell lines that induces apoptosis in lymphocytes. A marked reduction in the viability of the target splenocytes was evident after coincubation with the supernatants from various pancreatic adenocarcinoma cell lines (human, hamster, and murine). The immunocytolytic effect was not evident with the conditioned media of normal pancreatic duct epithelial cells or other nonpancreatic tumor cells. Biologic activity of the supernatants was determined to be heat sensitive and reside in a 30- to 50-kDa range. Immune and functional assays have excluded known immunosuppressive factors.