This study analyzes the incidence and course of antibody-mediated rejection (AMR) in a cohort of 237 renal transplant patients followed for 30 +/- 20 months. Among these, 32 patients were considered to be at risk for AMR and received intravenous immunoglobulin (IVIg), either as preconditioning (Group A, n = 18) or at the time of transplant (Group B, n = 14). The prevalence of AMR was 27.8% in Group A, 57.1% in Group B and 3.9% in the remainder of the population. Although graft loss remains greater among AMR than for acute cellular rejection (ACR) or the overall transplant population, we have identified a good outcome group (GFR > 15 mL/min/1.73 m(2)) (n = 13), whose renal function at the end of follow-up was comparable to that of the general transplant population. The factors associated with bad outcome are: (1) immunologic: presence and/or persistence of donor-specific anti-HLA antibodies post-transplantation and (2) histologic: neutrophilic glomerulitis, peritubular capillary dilatation with neutrophil infiltrates and interstitial edema at the time of first biopsy; and at the time of late biopsy (3-6 months): lesions of vascular rejection, and monocyte/macrophage infiltrates in glomeruli and dilated peritubular capillaries. Persistence of C4d does not predict outcome. This study outlines for the first time the immunologic and histologic profiles of AMR patients with poor prognosis.