Seventeen cases of a histologically and clinically unusual renal acute dysfunction in kidney recipients, individualized among a population of 1378, are reported. The basic histological lesion was a huge capillary congestion, associated with capillary and arteriolar thromboses or parenchymal necrosis in most patients, and contrasting with the absence of the classical features of acute cellular rejection, i.e., tubulitis, glomerulitis, edema, and infiltrate. The corresponding clinical history was characterized by its early timing in the course of transplantation (< 3 months), its sudden occurrence in patients usually having good transplant function, leading to end-stage renal failure in a few days, and its resolution under rejection treatment. The occurrence of this syndrome was significantly linked with a good HLA matching: 13 of the 17 recipients were HLA-DR matched (P < 0.0001). The etiology of this syndrome remains unknown. There was no evidence for graft vessel thrombosis. Because of some histological similarities, the usual causes of the hemolytic uremic syndrome, including bacterial and viral infections or cyclosporine arteriolopathy, were discussed. Acute vascular rejection was suspected, but the cross-match was negative on T lymphocytes in all cases and anti-HLA class I and II antibodies were not found to develop at the time of transplant dysfunction, except in 1 patient, in whom the detected anti-DR antibodies were not directed at the kidney donor. Anti-human umbilical vein endothelial cell antibodies, detected in an antibody-dependent cellular cytotoxicity assay, were present in 6 patients (of the 14 tested) at the onset of renal failure, but they were either absent (n = 3) or already present at the time of transplantation (n = 5) in the other 8 patients. Therefore, reliable arguments are lacking to conclude that this acute transplant dysfunction is an acute vascular rejection and its strong association with HLA matching has, as yet, no satisfactory explanation.