Anti-glomerular basement membrane (GBM)-mediated glomerulonephritis (anti-GBM GN) plays a vital role in autoimmune diseases such as Goodpasture’s syndrome. Binding of autoantibodies to GBM results in complement activation and recruitment of inflammatory cells, which leads to glomerular inflammation and ultimately loss of renal function. Anti-GBM GN often results in end-stage renal failure despite therapy with plasma exchange and immunosuppressive drugs. There is an unmet medical need for development of novel therapies. We have generated a novel recombinant, soluble, truncated version of human complement receptor 1 (CR1) comprising the first three long homologous repeats (LHRs) (designated as HuCR1[1392]). This truncated soluble CR1 has increased inhibitory activity in various in vitro complement activation assays compared to the full-length soluble CR1. The ability of HuCR1[1392] to prevent damage mediated by kidney-bound antibodies was investigated in a mouse model of anti-GBM GN. Anti-GBM disease was induced in mice by injection of subnephrotic dose of rabbit anti-mouse GBM polyclonal antibody, followed six days later by administration of a mouse anti-rabbit IgG monoclonal antibody. HuCR1[1392] administered between these antibody injections significantly diminished albuminuria induced by the injections of the anti-GBM and the secondary antibodies. This was accompanied by a significant reduction in the deposition of the complement membrane attack complex (MAC) and diminished recruitment of neutrophils to the glomeruli. These preliminary results suggested that HuCR1[1392] could have potential beneficial effects in the treatment of anti-GBM diseases.