Background: Polymorphisms within the interleukin‐1 cluster are known to be associated with adult periodontal disease. However, interactions of genetic with other risk factors, especially smoking, remain questionable. The aim of this cross‐sectional study was to evaluate the genetic influence on periodontal variables in relation to environmental factors.Methods: One‐hundred fifty‐four (154) Caucasian subjects were clinically and radiographically assessed for their periodontal status, their smoking history recorded, and their allelic pattern of IL‐1α, IL‐1β, and IL‐1RN polymorphisms determined by genotyping.Results: In assessing periodontitis with mean probing depth, mean attachment loss, or mean bone loss, no differences were found in allele frequencies or combined allotypes between subjects with mild or moderate versus those with severe signs of periodontitis. However, the extent of attachment loss defined as percentage of sites >4 mm was signifi‐cantly associated with the composite genotype of IL‐1α/1β in smokers (odds ratio [OR] = 4.00; 95% confidence interval [CI] 1.03 to 16.70; P = 0.02). No differences were found in genotype negative subjects irrespective of their smoking status. They had nearly identical attachment loss as genotype positive non‐smokers. Similar non‐significant results were found with respect to extent of bone loss. An increased risk of more extended attachment loss was observed also in individuals carrying mutations of the combined genotype IL‐1α/IL‐1RN, again showing enhanced risk only in genotype‐positive and smoking subjects.Conclusions: The results provide evidence that the composite genotypes studied show interaction with smoking, the main exposition‐related risk factor of periodontal disease. Non‐smoking subjects are not at increased risk, even if they are genotype‐positive. J Periodontol 2002;73:27‐32.