Interleukin (IL)-1 alpha, IL-1 beta and IL-1 receptor antagonist (ra) play a major role in regulation of the inflammatory response in periodontal tissues. The aim of this study was to investigate the distribution of genetic variation in the IL-1 gene family among periodontitis patients and controls, taking into account smoking and microbiology as additional variables. There were 53 non-smoking and 52 smoking patients with severe adult periodontitis and 53 periodontal healthy controls genotyped for genetic variation in the IL-1 gene family. The presence of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans was established by culture techniques. A higher frequency of genotype+ (IL-1A*2 + IL-1B*2 + IL-1RN*2) was found in non-smoking periodontitis patients in whom P. gingivalis and A. actinomycetemcomitans could not be detected (42.1% vs. 11.3% in controls; p = 0.0068; or 5.7, 95% ci: 1.6-19.8). This data provide evidence that polymorphisms in genes of the IL-1 family are associated with severe adult periodontitis and may be a risk factor for severe periodontitis.