The light- and electron microscopic changes in the glomeruli of the rat's kidney have been investigated in the course of ageing and after subtotal nephrectomy, constriction of the renal vein, and intoxication by N-nitrosomorpholine. In spite of the fact that four different experimental models have been used, identical changes were always found in the glomeruli. Morphologically they consisted of a diffuse thickening of the glomerular basement membrane and of an increase in the mesangial matrix without a proliferation of the glomerular cells. Despite this thickening of the glomerular basement membrane, functionally an increased permeability of the glomerular capillaries for macroproteins could be observed, shown by a moderate proteinuria. For these morphological changes the term "glomerulosclerosis" is suggested; they are interpreted as a non-specific, non-inflammatory reaction of the glomerulus to an impairment caused by a number of varied influences. From the study of the formal pathogenesis of the glomerulosclerosis presented here one can conclude that in the individual experimental models the same result has been achieved in different ways. One possibility in the development of glomerulosclerosis is an increased production of the components of the basement membrane and of the mesangial matrix. This is the pathway which appears to be followed after nephrectomy. Another possibility is a slowing down of the breakdown of both the matrix and the membrane. This seems to be the case in the glomerulosclerosis occuring in the course of ageing, and after hypoxic and toxic changes. It could be accounted for by a functional disturbance of, presumably, the mesangial cells responsible for the breakdown of the basement membrane and of the matrix. On the other hand, one may have to consider a primary alteration of the macromolecules of these structures, as is already known from studies of the, chemically closely related, collagen. The light- and electron microscopic studies of the normal and of the altered glomeruli have led to certain conclusions concerning the origin and the fomation of the glomerular basement membrane and the mesangial matrix. In order to widen the scope of the studies, additional autoradiographic investigations with 3H-proline and 3H-leucine have been performed in ultrathin and semithin sections of the rat's glomeruli. The results of the studies presented here suggest that of the three cell types of the glomerulus the visceral epithelial cells (podocytes, "Deckzellen") may participate on the formation of the glomerular basement membrane, whereas the mesangial cells appear to be responsible for the synthesis of the mesangial matrix.