Several studies have shown a role for interleukin-1 gene cluster polymorphisms in the risk assessment for periodontal diseases. In the Study of Health in Pomerania (SHIP), 3148 subjects were randomly selected from the population and assessed for a broad range of diseases and environmental/behavioral risk factors. From the complete study group in the age 40 to 60 years, N = 1085 subjects were genotyped for the interleukin-1 genotype composite polymorphism in relation to periodontal parameters. The study objective was to elucidate the gene-environment interaction between the risk factors smoking and IL-1 polymorphism. An increased risk of periodontal disease was found for IL-1 genotype-positive smokers: odds ratio adjusted for age, sex, education, and plaque OR = 2.50 (95% C.I. 1.21 to 5.13; p = 0.013). This was not the case with subjects who never smoked: OR = 1.09 (0.73-1.62; p = 0.676). These results support the hypothesis of gene-environmental interaction in periodontitis.