The serum of patients with membranoproliferative glomerulonephritis (MPGN) often exhibits C3 nephritic factor activity (C3NeF) associated with autoantibodies directed against the C3bBb alternative complement pathway C3 convertase. In the present study, we have sequentially assessed C3NeF activity in the purified IgG fraction of the serum of a patient with MPGN type II and end-stage renal disease every month for 1 year following renal transplantation and bilateral nephrectomy. C3NeF activity in the patient's purified serum IgG decreased with time from the first month after transplantation and became undetectable after forty-five weeks. At that time, plasma levels of C3 and factor B had returned to normal values. The disappearance of C3NeF activity in patient's IgG was selective in that no change in activity of two other autoantibodies and of one antibody against a non-self antigen was observed with time, indicating that the decrease in C3NeF activity was not related to a non-specific effect of immunosuppressive therapy. Loss of C3NeF activity was not related to the generation of anti-idiotypic antibodies against C3NeF. This study documents for the first time the selective disappearance of C3NeF activity following renal transplantation and bilateral nephrectomy. The results suggest that the autoantibody represents an antigen-driven expansion of self reactive B cell clones in response to a specific disease process in the kidney of patients with MPGN.