Bactericidal/permeability-increasing protein (BPI) is a member of the pattern recognition receptors of the innate immune system and recognizes lipopolysaccharides (LPS), a bacterial component belonging to the pathogen-associated molecular patterns (PAMPs). BPI mediates the neutralization of LPS and increases the phagocytosis and cytotoxicity against bacteria. Recently, the functionally effective polymorphism A645G resulting in the amino acid alteration Lys216Glu has been described. The aim of the study was to investigate the association of the A645G polymorphism with chronic periodontal disease. The study population comprised 123 patients with periodontal disease (36 with mild, 52 with moderate and 35 with severe periodontitis) and 122 healthy, unrelated control individuals. Genotyping of the BPI gene polymorphism A645G (Lys216Glu) was performed by polymerase chain reaction and restriction fragment length polymorphism analysis. Statistical analysis was carried out employing the chi(2) test with Yates correction. Genotype and allele frequencies of the polymorphism tested herein showed no significant differences between periodontal disease as compared to the control group. The frequencies of the G allele were 52.4% in patients with periodontal disease and 49.2% in the control individuals (P = 0.528). Moreover, no significant associations could be detected after stratification for disease severity and according to gender. The present study does not give evidence for the contribution of the BPI gene to the genetic background of chronic periodontal disease.