Endogenous digoxin-like substance (EDLS) in urine has been considered to be the representative of the natriuretic hormone, the endogenous inhibitor of the sodium pump (the sodium-potassium transporting enzyme Na, K-ATPase). Its site of production remains unknown, and so does its chemical nature. It has been suggested however that EDLS and the atrial natriuretic factor represent two distinct natriuretic system. Although the present work does not provide evidence for EDLS to be a natriuretic hormone, it nevertheless supplies data in support of this hypothesis. In preterm neonates, the decreased sodium excretion during the first days of life is accompanied by a parallel decrease in urinary EDLS excretion. The same was observed in a group of children from the infant period through the age of 12-14 years. Both parameters showed in parallel the lowest values in the oldest children examined. Children aged 8-12 years also showed parallel excretion of sodium and ELDS, even if natriuresis was induced in recumbent position and antinatriuresis in upright position. When the children remained recumbent for 24 h there were no differences in sodium and EDLS excretion between daytime and night. Children involved in adequate physical activities during daytime excreted less sodium and EDLS during the day than at night.