The effects of uninephrectomy on the function and structure of the remnant kidney were assessed in rats with Adriamycin-induced nephrosis, 12 weeks after the injection of Adriamycin. The kidney volume of Adriamycin-treated uninephrectomized rats (NX-AD) was 2.3 times that of sham-operated, Adriamycin-treated animals (SH-AD; p < 0.001). The marked renal enlargement in NX-AD animals was due to the development of large tubular cysts. Following uninephrectomy, the fractional volume of tubular lumen almost doubled (NX-AD, 0.33 +/- 0.02; SH-AD, 0.17 +/- 0.02; p < 0.001) and the absolute volume of tubular lumen increased more than fourfold (NX-AD, 0.51 +/- 0.08 ml; SH-AD, 0.12 +/- 0.02 ml; p < 0.001). The frequency of tubular lumen with a large cross-sectional area (> or = 40,000 microns 2) was 5.8 +/- 1.1% in NX-AD and 0.7 +/- 0.2% in SH-AD groups (p < 0.001). The fractional volume of interstitial fibrosis in NX-AD animals was larger than in SH-AD (0.09 +/- 0.02 versus 0.04 +/- 0.01%, p < 0.05). As opposed to the worsening of tubulointerstitial disease, single-kidney glomerular filtration rate, fractional protein clearance, glomerular volume and the extent of glomerular sclerosis did not differ significantly in NX-AD as compared to SH-AD groups. This study shows that uninephrectomy in rats with Adriamycin nephrosis worsens interstitial nephrosis and aggravates the formation of tubular cysts, leading to a macrocystic kidney disease. These changes are not associated with an increase in glomerular sclerosis.