The pathophysiologic mechanisms underlying alcoholic chronic pancreatitis are poorly understood. Cytokines participate in the immunologic progression of acute and chronic pancreatitis and may play an important role in the development of pancreatic fibrosis. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at positions -308 and -238; in the transforming growth factor-beta 1 (TGF-beta(1)) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1082; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with alcoholic chronic pancreatitis. We investigated 42 patients with alcoholic chronic pancreatitis. We studied 94 control subjects for the TNF-alpha polymorphisms and 73 control subjects for the remaining polymorphisms. Mutation analysis was performed by direct DNA sequencing or by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The genotype frequencies were similar between patients and control subjects for all investigated cytokine polymorphisms (P>.05). We did not find an association between the different genotypes and the clinical course of the disease. Therefore, we assume that these genetic variants do not play a dominant role in alcoholic chronic pancreatitis.