Two doses of adriamycin (2 mg/kg i.v.) were administered to young adult rats with a 22‐day interval and the kidneys were examined 51, 79, and 107 days after the first injection. Light microscopy showed early prominent intraglomerular microcystic spaces and progressive, though not severe, segmental glomerulosclerosis with focal interstitial scarring and round‐cell infiltration. The main features of the ultrastructure were widespread fusion of foot processes, focal cytoplasmic rarefaction of podocytes, and non‐specific sclerosis of the mesangium without signs of severe degenerative changes or mesangiolysis. The Segmental microcystic structures corresponded to agglomerted intrapodocytic vacuoles. The scatter of glomerular polyanion sites visualized by polyethylenimine–phosphotungstic acid resembled that of control animals but the quantitative assessment revealed a significant reduction. CD4‐positive cells were the predominant element of the interstitial infiltrates. Most of the infiltrating cells expressed Ia antigens, whereas la‐positive intraglomerular resident mononuclear cells were depleted. The adriamycin lesion resembles the post‐five‐sixths nephrectomy ablation nephropathy in the subpopulations of the interstitial infiltrate but differs from it in the reduction of intraglomerular resident macrophages, the absence of destructive mesangial damage, and reduced segmental glomerulosclerosis. The main feature is the prolonged damage of podocytes, especially of their cytoskeletal system.