Adrenomedullin 2/intermedin (AM2/IMD) is a novel vasodilator peptide with various effects on the renal function and cardiovascular system. An exonic insertion (I)/deletion (D) polymorphism (rs3840963) may influence generation of AM2/IMD-53, due to its location within the N-terminal sequence. We investigated the association of this polymorphism with blood pressure, renal function and the risk of silent cerebrovascular lesions in a Japanese population recruited from the Ohasama study. We recorded 24 h ambulatory blood pressure (ABP), estimated glomerular filtration rate (eGFR) and proteinuria of 1073 individuals over 40 years of age. Silent cerebrovascular lesions (lacunar infarction and white matter hyperintensity (WMH)) were recorded in 794 individuals over 55 years of age. Chronic kidney disease (CKD) was diagnosed in individuals with proteinuria and/or decreased eGFR ≤60 ml min(-1) per 1.73 m(2). DD carriers, compared with II and ID carriers, displayed significantly higher 24 h ABP (127.4 vs. 122.0 and 122.9 mm Hg, respectively, in systolic ABP, P=0.009; and 74.8 vs. 71.3 and 72.5 mm Hg, respectively, in diastolic ABP, P=0.002), and lower eGFR (75.4 vs. 82.6 and 82.9 ml min(-1) per 1.73 m(2), respectively, P=0.04). DD carriers also had a significantly higher odds ratio (OR) for prevalence of CKD (OR: 2.7, P=0.003), presence of lacunar infarction (OR: 2.4, P=0.01) and WMH (OR: 2.7, P=0.003), compared with II carriers. The AM2/IMD I/D polymorphism is associated with renal dysfunction, blood pressure regulation and asymptomatic cerebrovascular diseases in the Japanese general population.