The effects of insulin on renal haemodynamics and renal sodium handling were studied in 10 healthy males. Using the euglycaemic insulin clamp technique, insulin was infused on separate days resulting in two levels of hyperinsulinaemia (41 +/- 3 and 90 +/- 7 mU/l, respectively). Renal haemodynamics and the proximal and distal tubular sodium handling were studied using inulin, para-amino-hippuric acid, sodium and lithium clearances. Low- and high-dose insulin infusions were followed by a fall in sodium clearance from 1.6 +/- 0.1 ml/min to 1.2 +/- 0.1 and 1.0 +/- 0.1 ml/min, respectively. Both levels of hyperinsulinaemia resulted in increased distal tubular sodium reabsorption. The distal antinatriuretic effect of insulin was associated with dose- and time-dependent decline in proximal tubular sodium reabsorption. The changes in proximal tubular sodium handling occurred without any significant changes in natriuretic factors, such as renal dopamine and plasma atrial natriuretic peptide levels. However, hyperinsulinaemia resulted in time- and dose-dependent increases in renal plasma flow, and renal vasodilatation could, possibly via changes in renal interstitial pressure, have contributed to the fall in the proximal tubular sodium reabsorption. The results also suggest that decreased proximal sodium reabsorption may be a compensatory mechanism counteracting the insulin-induced sodium retention.