Background: Idiopathic collapsing glomerulopathy (ICG) and HIV-associated nephropathy (HIV-AN) are characterized by severe nephrotic syndrome, collapse and sclerosis of the glomerular tuft with prominent podocyte alterations and extensive tubulointerstitial lesions. We previously showed phenotypic changes in podocytes from patients with diffuse mesangial sclerosis, a severe glomerulopathy sharing several morphological features with collapsing glomerulopathy. The aim of this study was to analyze the podocyte phenotype in ICG and HIV-AN. Methods: Using immunohistochemical techniques, we studied the podocyte expression of the transcription factor WT1 and its target PAX2, GLEPP1, synaptopodin and vimentin as markers of podocyte maturity and of proliferating cell nuclear antigen (PCNA) as a marker of proliferation. Apoptosis was analyzed by the TUNEL method. Results from renal biopsies of ICG and HIV-AN were compared with those obtained from normal kidney, minimal change nephrotic syndrome (MCNS), focal and segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). Results: Abnormal distribution of WT1 and PAX2 and extensive loss of podocyte markers were observed in ICG and HIV-AN; this dysregulation was associated with podocyte proliferation without detectable apoptosis. In contrast, no podocyte changes were detected in MCNS or MGN. In FSGS, phenotypic changes, without proliferation, were restricted to podocytes surrounding focal and segmental glomerular lesions. Increased PCNA expression and apoptosis were observed in ICG and HIV-AN tubular cells. Conclusion: Dysregulation of podocyte phenotype and proliferation are present in both ICG and HIV-AN. This suggests that, whatever their etiology, both types of collapsing glomerulopathy share a common pathogenic pathway. Upregulation of cell proliferation and apoptosis observed in tubular epithelial cells is probably involved in the occurrence of severe tubulointerstitial lesions in collapsing glomerulonephritis.