RBCs from one-third of IgA nephropathy patients examined had more IgA1 on their surface than cells from healthy volunteers. The amount of IgA1 on RBCs was estimated to be no more than 30 ng/4 x 10(8) RBCs. The level of IgG on the surface of RBCs from IgA nephropathy patients were the same as those from healthy volunteers. Free IgA1 myeloma protein binds poorly in vitro to RBCs from both an IgA deficient patient and healthy volunteers. Polyethylene glycol precipitate from the sera of IgA nephropathy patients bound to RBCs from an IgA deficient patient. Factor I did not release IgA1 bound to RBCs from IgA nephropathy patients. These results suggest that this binding is mediated through the interaction of IgA1 and RBCs, and that some alteration of the IgA1 molecule (complexes or aggregation) may account for this binding.