BACKGROUND The single-nucleotide polymorphisms (SNPs) of the phosphodiesterase 4D (PDE4D) and interleukin-1 (IL-1) genes are associated with increased risk for the development of ischemic stroke (IS) in whites. However, little is known about whether this association could also occur in Han Chinese. METHODS A total of 371 patients with IS and unrelated healthy controls were recruited and the SNPs of the PDE4D (83T/C), (87T/C), IL-1 (-889C/T) and IL-1 (-511C/T) were characterized, respectively, by polymerase chain reactions-restriction fragment length polymorphism (PCR-RFLP). The genotype and allele frequencies of these SNPs in this population were statistically analyzed. RESULTS The genotype and allele frequencies of the PDE4D (87T/C) and IL-1 (-511C/T) were similar between IS patients and controls. In contrast, the frequencies of CC genotype and C allele of the PDE4D (83T/C) and the T allele frequency of IL-1 (-889C/T) in IS patients were significantly higher than that in healthy controls (p=0.001, p=0.003 and p=0.02, respectively), independent of the conventional risk factors. The values of odds ratio (OR) reached at OR=1.603; 95%CI=1.032-2.489; p=0.036 for the CC genotype of the PDE4D (83T/C) and OR=1.913; 95%CI=1.621-2.375; p=0.034 for the TT genotype of the IL-1 (-889C/T), respectively. CONCLUSIONS the SNPs of the PDE4D (83T/C) and IL-1 (-889C/T) were associated with increased risk for the development of IS in Northern Han Chinese.