Immunohistologic studies in IgA nephropathy which have suggested activation of the alternative complement pathway prompted us to study serum complement components and control proteins in 28 patients with IgA nephropathy. Thirteen patients, 12 of whom were men, had or developed chronic renal failure (CRF) during 34 +/- 5 months of follow-up. These patients were more hypertensive and had heavier proteinuria than those with stable renal function. Their serum IgA concentrations were not different from patients with normal renal function. The prevalence of HLA antigens was similar to that for the reference population and BW35 was not associated with CRF. Serum C3, B, H and I concentrations in patients with stable normal renal function were higher than they were in patients with CRF. Four patients studied--two with normal renal function and two with CRF--had partial familial deficiencies of single complement proteins. Our data suggest that high serum levels of C3, B, H and I may be associated with stable normal glomerular filtration rate and that complement deficiencies are not infrequent in IgA nephropathy. How these findings relate to the pathogenesis and progression of IgA nephropathy requires further study. We also conclude that higher serum IgA concentrations and the presence of BW35 are not necessarily associated with progressive renal insufficiency in IgA nephropathy.