The pathophysiology of pancreatitis and the pancreatic stress response are not well understood. In the pancreas, mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) are reportedly regulated by secretagogue stimulation and hyperstimulation. However, no data exist on the expression and regulation of pancreatic p38 Map kinase. Pancreatic expression of p38 Map kinase and MAPK, SAPK and p38 regulation during pancreatic stress were investigated. For hyperstimulation and secretory stress, cerulein was given intravenously, while hyperthermia preconditioning stress was induced by whole body hyperthermia (42 C). In addition to MAPK and SAPK, p38 Map kinase was found to be expressed in the rat pancreas. Cerulein regulated all kinases time-and dose-dependently. MAPK and p38 Map kinase showed basal activity and were further activated at low cerulein doses. SAPK had no basal activity and its activation required maximal secretory to supramaximal amounts of cerulein. Cerulein hyperstimulation, inducing pancreatitis, activated p38 more rapidly than SAPK and more strongly than MAPK. In contrast to cerulein hyperstimulation stress, hyperthermia stress only activated p38 Map kinase. p38 Map kinase is expressed in the pancreas and is most rapidly activated following cerulein hyperstimulation. Both SAPK and p38 Map kinase are possibly important regulators during the onset of cerulein pancreatitis.