Background Previous research with normotensive adults aged over 40 years ('older') found that sensitivity of blood pressure of subjects with high resting end-tidal partial pressures of CO(2) to high sodium intake was greater than normal, Objective To test the hypothesis that the lesser sensitivity of blood pressure of young normotensive adults to high sodium intake is also a function of resting end-tidal partial pressure of CO(2), Design Forty-eight Caucasian men and women (age 28.5 +/- 1.4 years) had a lower than normal dietary intake of sodium chloride for 4 days, and then ingested sodium chloride capsules for 7 days tan additional 190 mmol/day sodium chloride), Resting end-tidal partial pressure of CO(2) and blood pressure, and 24 h ambulatory blood pressure, were measured before and after the high-sodium diet Overnight urine samples were collected before and after the high-sodium diet to determine dietary compliance, and to assess changes in urinary excretion of endogenous digitalis-like factors (a ouabain-like factor, and a marinobufagenin-like factor) that covary with plasma volume. Results Subjects with high end-tidal partial pressures of CO(2) had lower resting heart rates and lower urinary excretion of ouabain-like factor before sodium loading, Sodium loading decreased mean partial pressure of CO(2) (by 0.8 +/- 0.2 mmHg) and increased only ambulatory systolic blood pressure (by 2.1 +/- 0.8 mmHg) for the whole group, However, the changes in resting systolic (r = 0.32, P < 0.025) and diastolic (r = 0.36, P < 0.01) blood pressures and in 24 h systolic (r = 0.28, P< 0.05) blood pressure after sodium loading were ail positive functions of individual resting end-tidal partial pressures of CO(2), Sodium loading increased urinary excretion of marinobufagenin-like factor (by 1.78 +/- 0.88 nmol) and the magnitude of the individual increase was a function of end-tidal partial pressure of CO(2), Conclusions The results indicate that a high resting partial pressure of CO(2) augments the effects of high sodium intake on plasma volume, levels of endogenous digitalis-like factors, and blood pressure in young normotensive humans, I Hypertens 16:1015-1022 (C) 1998 Lippincott-Raven Publishers.