Background: It has been suggested that aggressive periodontitis (AgP) has a genetic basis, but this theory has not been confirmed. The intent of this investigation was to study whether specific interleukin (IL)‐1 genotypes and/or alleles could be used to predict susceptibility to generalized AgP (GAgP) in Chinese. Methods: The GAgP group consisted of 122 patients, and the control group included 95 healthy subjects. Single nucleotide polymorphisms at IL‐1A (+4845) and IL‐1B (–511, +3954) were analyzed by standard polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay. The polymorphism of a variable number tandem repeat (VNTR) in intron 2 of IL‐1RN was detected by PCR amplification and fragment size analysis. Results: There was no significant association of IL‐1 polymorphisms with GAgP in the unstratified subjects. However, when cases were stratified by gender, the frequencies of A2+ genotype and allele 2 at IL‐1A +4845 were significantly increased in male patients compared to male controls (genotype: odds ratio OR 5.58, 95% confidence interval CI: 1.09 to 28.68, P = 0.039; allele: OR 4.97, 95% CI: 1.01 to 24.50, P = 0.049; adjusted for age and smoking status). The frequency of IL‐1B –511 A1/A2 heterozygote was significantly increased in male GAgP group compared to male controls (adjusted OR 3.16, 95% CI: 1.01 to 9.89, P = 0.048). In females, no significant differences were found between patients and controls in corresponding analyses at all polymorphic loci. A possible combined effect of IL‐1B –511 polymorphism and smoking on the elevated risk to GAgP was observed. The OR of GAgP for combined A2+ genotype and smoking was 12.45 (95% CI: 1.43 to 108.06, P = 0.022), and for combined allele 2 and smoking was 18.25 (95% CI: 2.32 to 143.86, P = 0.006). Conclusions: The polymorphisms of IL‐1A +4845 and IL‐1B –511 may play an important role in determining GAgP susceptibility in Chinese males. Furthermore, a possible combined effect of the polymorphism of IL‐1B –511 and smoking on GAgP susceptibility was suggested. J Periodontol 2004;75:1627‐1635.