Pancreatic diseases represent a major, poorly treated health-care problem in the United States Unfortunately, once established the devastating effects of severe acute pancreatitis or chronic pancreatitis cannot be reversed. We believe true advances in the treatment of pancreatic disease, as in other diseases, rest in the early identification of at-risk individuals and in the prevention or limitation of the disease. Herein we propose a national study to determine the regional prevalence of major pancreatic diseases classified according to the TIGAR-O system, to determine the underlying genetic variations and immune markers associated with pancreatitis, and to develop a major biological and phenotypic resource for future investigations. This approach utilizes innovative, high-throughput gene analysis technologies to assist in genotype-phenotype correlation, prognostication and risk assessment. Our Specific Aims are as follows. Aim 1: To establish a national network of centers with expertise in pancreatic disease for the recruitment and follow-up of patients with recurrent acute and chronic pancreatitis with spouse, age and race matched controls, and sib/parent controls, and to develop a biologic repository for further study. Aim 2: To determine the prevalence of known genetic variations and autoimmune markers associated with recurrent acute and chronic pancreatitis. Aim 3: To describe the interaction of environmental and genetic factors in the expression of the clinical manifestations of chronic pancreatitis and risk of pancreatic cancer. The results of these studies may result in the development new diagnostic tools that can be applied at the onset of symptoms, and rational therapy to prevent the development of those pancreatic diseases that we cannot currently cure.