Summary: Although a genetic predisposition to IgA nephropathy can be documented in a minority of patients, the majority of cases are sporadic. The frequent association with mucosal infections suggest the aetiologic involvement of microbial antigens. However, no particular bacterial or viral strain has clearly been implicated. The involvement of mesangial or endothelial autoantigens has been suggested but not proven in a majority of cases. Most patients have a significantly higher memory repertoire of IgA forming B-lymphocytes in their bone marrow associated with high plasma levels of IgA1 while the mucosally stimulated IgA response against recall antigens is augmented, the mucosal and plasma IgA response after mucosal stimulation by neoantigen is significantly reduced or absent. These observations suggest that IgA nephropathy patients have a defect in raising a mucosal IgA response against novel microbial antigens and that they will suffer from recurrent mucosal infections until they have developed a large enough repertoire of memory B-cells to protect their mucosal surfaces. As a consequence of the recurrent stimulation of the IgA immune system, high levels of plasma IgA are found. The mechanism of IgA deposit formation in the mesangium is unknown. The ensuing inflammatory reaction in the glomeruli may vary from mild to severe, but usually the disease has an indolent course. The progression of IgA nephropathy to renal failure is clinically the most important complication. Recent observations on the role of cytokines in the pathogenesis of interstitial infiltration, interstitial fibrosis and tubular atrophy have created the opportunity to study and manipulate the process of renal scarring and the progression to renal failure.