A study was made of the content of lymphocyte subpopulations and activation marker expression on peripheral blood mononuclear cells. There were 15 patients with diabetic nephropathy (DN) in the pre-nephrotic stage and 19 patients with lingering diabetes mellitus (DM) not complicated by DN. Indirect immunofluorescence and monoclonal antibodies to leukocytic differentiated antigens CD3, CD4, CD8, CD22, CD25, CD71 and HLA-DR were used. Radioimmunoassay was employed simultaneously to measure the content of neopterin (a marker of cellular immunity activation) in the serum. It has been demonstrated that the pre-nephrotic stage of DN is marked by the normal content of the main subpopulations of peripheral lymphocytes (CD3, CD4, CD8 and CD22-positive). At the same time DN is associated with hyper-expression of activation markers (CD25, HLA-DR) on peripheral blood mononuclear cells and with an increase of serum neopterin concentration. The pathogenetic role of activated lymphocytes in DN may be related to the production by them of endoglycosidase, an enzyme splitting heparan sulfate of the subendothelial basal membranes of the glomeruli, thereby interfering with the negative charge of the glomerular filter and the local anticoagulation potential.