The gene for natriuretic peptides receptor C (NPRC), which is a candidate susceptibility gene for essential hypertension (EH) or obese hypertension, plays a key role in the regulation of plasma levels and biological effects of natriuretic peptides. The aims of the present study were to find new genetic markers in the 5′-flanking region of the NPRC gene and to assess relationships between variants and phenotypes of EH, including EH in obese patients. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we discovered a novel six-nucleotide repeat polymorphism located 4 base pairs (bp) upstream of the major transcriptional initiation site. We performed association analysis of this variable number of tandem repeat (VNTR) in 242 EH patients and 212 normotensive controls (NT). Although no significant difference in overall frequency of VNTR was found between NT and EH groups, the blood pressure level of EH patients with the 5/6 genotype was significantly higher in obese subjects. This suggests that the VNTR of the 5′-flanking region of the NPRC gene influences blood pressure levels in obesity-associated hypertension.(Hypertens Res 2004; 27: 711–716)