Increased brain natriuretic peptide (BNP) expression in the ventricles antedates elevated blood pressure (BP) in experimental studies. We hypothesized that higher plasma BNP levels in nonhypertensive individuals may be associated with a greater likelihood of future BP increase and/or hypertension. We evaluated the relations of plasma BNP to longitudinal BP tracking and incidence of hypertension in 1801 nonhypertensive Framingham Heart Study participants (mean age, 56 years; 57% women) by using gender-specific multivariable logistic regression. Progression of BP stage was defined as an increment of one or more BP categories, as classified by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Hypertension was defined as a systolic BP > or =140 or diastolic BP > or =90 mm Hg or use of antihypertensive medications. On follow-up 4 years from baseline, progression of BP category was observed in 36.2% of men and 33.1% of women; hypertension developed in 16.4% of men and 15.5% of women. In multivariable models adjusting for known risk factors, elevated plasma BNP level was associated with increased risk of BP progression in men (odds ratio of 1.15 for trend across categories, P=0.046) but not in women (P=0.82). There were no significant trends of increasing incidence of hypertension across BNP categories in men or women. In our community-based sample, higher plasma BNP levels were associated with increased risk of BP progression in men but not women. Additional investigations are warranted to confirm these findings and elucidate the basis for these gender-related differences.