Immunoglobulin A-fibronectin aggregates (IgAFNs) may be demonstrable in the serum of patients with IgA nephropathy. Initial reports suggested that IgAFN could be a marker for IgA nephropathy with clinical utility in differentiating IgA nephropathy from non-IgA glomerulonephritis. Serum IgAFN concentration was determined in 105 samples from 52 patients with IgA nephropathy who were followed in Kentucky or Tennessee. On at least one occasion, IgAFN was positive (significantly elevated) for 25 of the 52 patients (48%). Thirty-eight percent of the 105 samples were positive. Pediatric and adult patients had a similar incidence of positive IgAFN. A small but nonsignificant increase in the incidence of positive IgAFN was shown for patients who had or subsequently developed chronic renal insufficiency. Weak but significant correlations were found between IgAFN concentration and serum IgA concentration and C3 activation. In the present study, IgAFN concentration was significantly higher for the patients with IgA nephropathy as compared with the patients with non-IgA glomerulonephritis from our previous study. While IgAFN may be clinically useful in differentiating IgA nephropathy from non-IgA nephropathy, the present assay cannot be used to diagnose IgA nephropathy. © 1993, National Kidney Foundation. All rights reserved. All rights reserved.