The mesangium of the glomerular capillary ultrafilter is a specialized pericapillary tissue. In adult mammals its location is limited to the axial portions of the loop, but it extends peripherally to encircle the capillary in the fetal state and in certain glomerular diseases. It contains predominantly intrinsic mesangial cells, which resemble contractile endocytic capillary pericytes, and which are embedded in the extracellular matrix. In addition, the mesangial space normally harbors few resident Ia-antigen bearing, immune-competent cells and rare transient monocyte-macrophages. Due to its unique location between the fenestrated endothelial lining of the capillary lumen and the glomerular basement membrane, constituting the filtration barrier, the mesangium is prone to deposition of potentially noxious plasma constituents and filtration residues, such as phlogogenic foreign proteins and immune complexes. The determinants of the mesangial entry, uptake and removal of such materials are presently incompletely understood but they are thought to include the amount and nature of the deposit, local hemodynamic factors and the ability of the mesangium to degrade or to eliminate the deposited agent. Histopathologic studies of various human and experimental glomerular diseases reveal that increased mesangial cell proliferation and matrix widening may occur either in direct response to deposits or induced by mediators released from inflammatory cells, such as monocyte-macrophages. While the functional damage to the glomerular filter is usually mild when the reaction is limited to the mesangial space, it is more pronounced when the mesangial abnormalities are secondary to subendothelial deposits of the peripheral capillary wall. Recent experimental data indicate that a mesangial inability in removing deposited material may develop in certain chronic glomerular disorders characterized by marked proteinuria, glomerular hypertension and hyperfiltration or accumulation of matrix material. Such states of mesangial dysfunction may play a critical role in the pathogenesis of progressive glomerular sclerosis. It is concluded that better understanding of the pathophysiology of the mesangium would be valuable for designing more effective diagnostic and therapeutic approaches to patients with glomerular disease.