In order to evaluate whether insulin-dependent diabetes mellitus patients with incipient nephropathy have an overactivity of erythrocyte sodium-lithium countertransport (Na+/Li+ CT), 82 diabetic children and 38 healthy age-matched control subjects and their parents and grandparents were studied. The children were divided into two groups according to the presence of persistent microalbuminuria (MA). Diabetic children with MA had Na+/Li+ CT activity higher than normoalbuminuric diabetics and healthy controls. The parents and grandparents of microalbuminuric patients showed higher Na+/Li+ CT than parents and grandparents of normoalbuminuric diabetics and of the controls. This study demonstrates that predisposition to hypertension, as indicated by increased Na+/Li+ CT activity in erythrocytes, is more frequently detectable in patients with persistent microalbuminuria than in diabetics without persistent microalbuminuria or in healthy controls. Overactivity of Na+/Li+ CT is present also in parents and grandparents of diabetic children with MA. This study suggests that genetic predisposition to hypertension is more frequent in patients at risk of developing diabetic nephropathy, as well as in their parents and grandparents.