Significant levels of EAC-rosette inhibition compared to control subjects were found in the sera of patients with focal and segmental hyalinosis (FSH), membranoproliferative glomerulonephritis (MPGN) and extra-membranous glomerulonephritis (EGN). In patients with IgA disease, although some sera produced high levels of inhibition, the group as a whole did not differ significantly from the controls. Evidence was obtained suggesting that the rosette inhibitory activity was due to immune complexes (IC) bearing C3 rather than C3 fragments. Firstly, the inhibitory activity was precipitable by 4% PEG, a concentration which does not precipitate the C3 fragments. Secondly, the inhibitory activity was selectively removed from the PEG precipitates by an anti-human immunoglobulin G immunoabsorbent. Finally, since it had been suggested that in some instances an unknown serum factor could inhibit EAC-rosette formation and activation of the alternative pathway of complement, the latter was studied and found to be normal in all the sera studied. Taken together, these results suggest that the inhibition of EAC-rosette formation obtained with the sera of the patients studied was due to the presence in these sera of some material behaving as IC. No clear-cut association was, however, seen between rosette inhibition and the presence or absence of Ig or C3 deposits in the kidney.