Animal and human data suggest a link between endogenous acid production with elevations in blood pressure and the development of hypertension; increases in endogenous organic acid production can lead to a higher anion gap. We studied the cross-sectional association between the serum anion gap and blood pressure among 1057 non-diabetic patients who were not taking antihypertensive drugs, and who received their care at a multisite, multispecialty group practice in eastern Massachusetts. Using linear regression controlling for age, sex, race, BMI, estimated GFR and presence of impaired fasting glucose, every 1 mEq l(-1) higher serum anion gap was associated with a 0.27 mm Hg (P=0.08) higher systolic, 0.20 mm Hg (P=0.05) higher diastolic and 0.22 mm Hg (P=0.04) higher mean arterial pressure; these results suggest that endogenous acid production may raise the risk of hypertension.