To investigate whether constitutive alterations of the Na+/H+ antiport or of cell proliferation control mechanisms are implicated in development of nephropathy in insulin-dependent diabetics (IDD), skin fibroblasts from controls, recent-onset IDD with normal or high glomerular filtration rates, and IDD with proteinuria were cultured by explant technique. The Na+/H+ antiport activity was studied using the pH sensitive fluorescent dye BCECF. The cell growth capacity was investigated by determination of cell DNA doubling time and by nuclear [3H]thymidine incorporation in response to serum. The Na+/H+ antiport activity and fibroblast growth capacity did not differ between fibroblasts from controls and IDD patients, suggesting the absence of a genetic alteration of the Na+/H+ antiport in the development of diabetic nephropathy.