In this study, endogenous digoxin-like substance within the plasma was measured by radio-immunoassay in 122 children with the systolic blood pressure equal to or greater than the 75th percentile (age = 12.3 +/- 2.5 years) and 136 children with the systolic blood pressure at or less than the 50th percentiles (age = 11.9 +/- 2.8 years) after a follow-up of one year. The levels of digoxin-like substance in the plasma of children with the higher blood pressure were much higher than those in the controls (32.7 +/- 17.3 versus 22.7 +/- 12.7 pg/ml, P less than 0.001) and were positively correlated to the blood pressure (r = 0.21, P less than 0.05 for systolic blood pressure; and r = 0.41, P less than 0.01 for diastolic), and to the sodium content of the red cells (r = 0.36, P less than 0.001), plasma (r = 0.25, P less than 0.01) and 8-hour overnight urinary output (r = 0.32, P less than 0.05). The children in the group with higher blood pressure exhibited an exaggerated natriuresis after an oral saline-water load. We believe that a circulating inhibitor of sodium transport may play an important role in the early stage of the evolution of hypertension.