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Recent studies have shown that high resting end tidal CO2 (P ECO2) is a marker for blood pressure sensitivity to high sodium intake by normotensive humans. The present study investigated the association of resting P ECO2 with resting blood pressure in participants in the Baltimore Longitudinal Study on Aging (BLSA).P ECO2 of 314 healthy participants (153 men and 161 women, aged 21–79 years) was measured by a respiratory gas monitor during 25 min of seated rest, and blood pressure every 5 min by an automated oscillometric system. The independent associations of P ECO2 and other variables with systolic (SBP) and diastolic (DBP) blood pressure were analysed via multiple regression. Sex differences in age-associated changes in P ECO2 and in the role of pulmonary capacity in the P ECO2-blood pressure relationships were also studied.Resting P ECO2 was an independent predictor of SBP in women (β=0.215; P < 0.0015; overall r2 = 0.27; P < 0.0001), and accounted for more than 10% of the variance in SBP in women over age 50 years. No such associations of P ECO2 with SBP of men, or with DBP of men or women, were observed. P ECO2 was lower in younger women (36.0 ± 0.9 mmHg) than in younger men (40.4 ± 2.0), but higher in older women (37.1 ± 0.5) than in older men (35.5 ± 0.4).P ECO2 is an independent determinant of resting SBP in women, especially those aged 50 years or more. The origin of individual differences in resting P ECO2 and its possible role in the development of chronic hypertension remain to be clarified.