Glomerular function and structure were assessed after reduction of nephron number and restriction of protein intake in rats with adriamycin nephrosis. Rats received an injection of adriamycin and were divided into three groups with similar values for albuminuria after 4 wk. Group 1 rats then served as controls, group 2 rats were subjected to four-fifths renal ablation, and group 3 rats were placed on a low protein diet (8% protein) while group 1 and group 2 rats remained on a standard diet (24% protein). Micropuncture and morphometric studies were performed 10 d later. Estimated single-nephron albuminuria (SNalb) was increased by renal ablation in group 2 and decreased by protein restriction in group 3 (group 1, 20 +/- 2 micrograms/d; group 2, 68 +/- 7 micrograms/d; group 3, 12 +/- 1 microgram/d, P less than 0.05 groups 2 and 3 vs. 1). Increased SNalb was associated with increased glomerular volume in group 2 and reduced SNalb was associated with reduced glomerular volume in group 3. (group 1, 1.44 +/- 0.04 x 10(6) microns 3; group 2, 1.66 +/- 0.08 x 10(6) microns 3; group 3, 1.26 +/- 0.03 x 10(6) microns 3, P less than 0.05 groups 2 and 3 vs. 1). Increased SNalb in group 2 was not associated with an increase in glomerular transcapillary hydraulic pressure. The area of epithelial cell detachment from the peripheral capillary wall was markedly increased in group 2 but not perceptibly altered in group 3 (group 1, 16 +/- 5 x 10(2) microns 2; group 2, 65 +/- 17 x 10(2) microns 2; group 3, 18 +/- 5 x 10(2) microns 2; P less than 0.05 group 2 vs. 1). These studies show that glomerular hypertrophy is associated with increased epithelial cell detachment from the peripheral capillary wall and with increased remnant nephron albuminuria after reduction of nephron number in rats with established nephrosis.