Children of parents with hypertension are at increased risk of developing high blood pressure. We hypothesize that circulating concentrations of putative biomarkers (that may play a role in development of high blood pressure) are higher in nonhypertensive offspring of parents with hypertension. We compared concentrations of 4 different biomarkers (urinary albumin:creatinine ratio, circulating C-reactive protein, aldosterone:renin ratio, and plasminogen activator inhibitor-1) in nonhypertensive Framingham offspring study participants with none (n=233), 1 (n=474), or both (n=322) parents with hypertension. Parental hypertension was defined as onset before age 60 years, based on longitudinal observations of the original Framingham cohort. Serum C-reactive protein concentrations were higher in nonhypertensive offspring with 1 (median: 1.7; Q1 to Q3: 0.8 to 3.6 mg/L) or both parents with hypertension (median: 1.8; Q1 to Q3: 0.7 to 3.6 mg/L) compared with offspring without parental hypertension (median: 1.4; Q1 to Q3: 0.7 to 3.2 mg/L). In multivariable analyses, parental hypertension was associated with higher serum C-reactive protein concentration in offspring (15% increase per parent with hypertension; P=0.004). Prospectively, the relation of parental hypertension to longitudinal changes in blood pressure in the nonhypertensive offspring was attenuated on adjustment for C-reactive protein (P=0.04 for attenuation). The levels of the other biomarkers evaluated did not significantly differ in offspring according to parental hypertension status. In conclusion, serum C-reactive protein concentrations are higher in nonhypertensive offspring of parents with hypertension. These data suggest that inflammation may partly mediate the familial influences on hypertension risk.