Multiple factors interact during the evolution of renal diseases. In the present study, we examined the expression of DNA topoisomerases type I and IIα, which reflect gene transcription and DNA replication, respectively. Enzyme content was assessed by immunohistochemistry using two specific monoclonal antibodies, C21 and Ki-S4, on 81 archival punch-biopsy specimens from patients with renal diseases, including minimal change disease (MCD; n = 10), focal segmental glomerular sclerosis (FSGS; n = 6), mesangial proliferative glomerulonephritis (MPGN; n = 11), membranous glomerulonephritis (MGN; n = 10), mesangial capillary glomerulonephritis (MCGN; n = 7), rapidly progressive glomerulonephritis (RPGN; n = 12), lupus nephritis (LN; n = 15), and tubulointerstitial nephritis (TIN; n = 10). Both enzymes were strongly expressed in diseases tending to rapid progression, notably RPGN and LN, whereas MCD and MGN showed Iow protein levels in both the glomerular and tubular compartments. Moreover, topoisomerase expression was significantly associated with the density of monocytogenic infiltrates (monitored by means of the monoclonal antibody KI-M1p), such pathogenesis-associated factors as antinuclear antibodies and paranuclear antineutrophilic antibodies, and serum immunoglobulin levels. There also was a positive correlation with serum creatinine levels and an inverse association with proteinuria and nephrotic syndrome. We conclude that the expression of DNA topoisomerases may be linked to pathogenetic mechanisms and may provide prognostic information. Because of their comparatively low nephrotoxicity, topolsomerase inhibitors might prove to be useful therapeutic agents in the treatment of renal diseases.