The interleukin 1 (IL-1) gene cluster has been implicated in acute pancreatitis. Penta-allelic and bi-allelic polymorphisms exist in the IL-1RN and IL-1B genes, respectively. The aim of the study was to investigate these polymorphisms in acute pancreatitis. Genotype and allele frequencies were determined in patients (n = 116) and healthy controls (n = 170) using the polymerase chain reaction. PCR products from the IL-1B study were further digested with Taq I restriction endonuclease. Patients were categorised according to aetiology, severity, and organ-failure scores. Allele 1 of the IL-1RN polymorphism was significantly increased in patients compared with controls (72.0 vs. 63.0%; p = 0.029, Pc = 0.029), in severe cases compared with controls (81.9 vs. 63.0%; p = 0.002, Pc = 0.004), in idiopathics compared with controls (82.4 vs. 63.0%; p = 0.002, Pc = 0.006), and in severe cases compared with mild cases (81.9 vs. 67.5%; p = 0.023, Pc = 0.046). Allele 2 was significantly decreased in severe cases compared with controls (18.1 vs. 33.0%; p = 0.013, Pc = 0.026), in idiopathics compared with controls (17.6 vs. 33%; p = 0.013, Pc = 0.039), and in severe cases compared with mild cases (18.1 vs. 32.5%; p = 0.023, Pc = 0.046). No significant differences were found for the Taq I allele or genotype frequencies between controls and patients/subgroups of patients. IL-1RN appears to determine severity of acute pancreatitis and susceptibility to idiopathic acute pancreatitis. No association was found between IL-1B and the disease.