Recent experimental data suggest a role for lipids in the pathogenesis of glomerulosclerosis. In this study, we examined the main apolipoproteins (apo) of high density lipoproteins (A-I, A-IV, E), low density lipoproteins (B), and very low density lipoproteins (B,E) in plasma and kidney tissue of rats with puromycin aminonucleoside or adriamycin nephrosis. In full-blown nephrosis, plasma concentrations of apo A-I and apo B were significantly elevated, apo A-IV and apo E levels did not change. Immunohistological studies in plastic sections revealed increased apo A-I, apo A-IV, and apo E immunoreactivity in glomerular visceral epithelial cells both in puromycin aminonucleoside and adriamycin nephrosis. This was confirmed by immunoelectronmicroscopy. In addition, apo B and apo E were encountered in increased amounts in the mesangium and colocalized with Oil Red O-positive lipid deposits, particularly in puromycin aminonucleoside nephrosis rats. Double-staining showed a preferential localization of apo B and apo E at sites of increased mesangial matrix in close proximity to ED1-positive foam cells, i.e., the mesangial macrophages. The close topographic association between apo B and apo E, lipid deposits, and macrophages in the mesangium lend further support to the concept of lipid-mediated glomerular injury in nephrosis.