The associations between renal tubular sodium handling and plasma levels of atrial natriuretic peptide, renin activity and aldosterone were studied in 295 untreated men under normal living conditions. The renal clearance of ingested lithium was used as a marker of proximal tubular sodium handling. Plasma atrial natriuretic peptide was inversely related to creatinine clearance (r = -0.148, P less than 0.01) and directly and significantly related to the overall fractional excretion of sodium (r = 0.213, P less than 0.001) and to distal (r = 0.151, P less than 0.01) fractional sodium excretion. Plasma renin activity was inversely related to sodium excretion at both proximal (r = -0.145, P less than 0.05) and distal (r = -0.236, P less than 0.001) tubular site, whereas plasma aldosterone was significantly and inversely related to distal sodium excretion only (r = -0.305, P less than 0.001). The association between plasma atrial natriuretic peptide and distal sodium excretion in a large sample of men under normal living conditions supports the view of a possible tubular effect of the hormone of the overall control of sodium excretion in man.