The normal architecture and function of the kidney are maintained by a critical turnover of the extracellular matrix (ECM). Although increased synthesis of ECM leads to progression of renal failure, the role of degradation of ECM by metalloproteinases in progressive nephropathies is unclear. Recently, in an animal model of membranous glomerulonephritis (Heymann nephritis), visceral epithelial cell (VEC) injury has been found to rapidly increase matrix metalloproteinase-9 (MMP-9) synthesis by these cells during the period of maximal proteinuria. Because injury to glomerular VECs may be an important initiating factor in the pathogenesis of focal segmental glomerulosclerosis (FSGS), especially in HIV-associated nephropathy (HIVAN), we determined the expression of MMP-9 and its inhibitors in renal biopsies of patients with HIVAN.