The levels of histone-reactive IgA antibodies in the sera of adult patients with IgA mesangial glomerulonephritis, membranous glomerulonephritis, membranoproliferative glomerulonephritis and idiopathic nephrotic syndrome (minimal change disease + segmental glomerulosclerosis + IgM nephropathy) were evaluated by an enzyme-linked immunosorbent assay. Increased levels of IgA antibodies to all five major histones (H1, H2A, H2B, H3, H4) were found in all four disease groups when compared to normal controls. These histone-reactive IgA antibodies were restricted to the IgA1 subclass and their levels did not correlate with the levels of total serum IgA, nor with serum creatinine, creatinine clearance, and 24-hour proteinuria. Increasing ionic strength resulted in only partial inhibition of the binding to histones and, in individual patients, levels of reactivity with individual histones were usually correlated. This study shows that elevated levels of IgA antibodies reactive with self antigens are present in primary glomerulonephritis and extends previous observations indicating that anomalies of the IgA system occur in various forms of primary glomerulonephritis and are not limited to IgA nephropathy.