It is claimed that antibodies to the vascular-endothelial (VEM) antigen system are responsible for early renal transplant rejection. To evaluate the significance of these anti-VEM antibodies, we performed a retrospective study in 16 patients aged 14.8 +/- 5 (SD) years, who received either a living-related HLA-identical (n = 5) or haplo-identical (n = 11) transplant between 4/79 and 3/84. All patients had been transfused prior to transplantation. Lymphocyte and monocyte complement dependent cytotoxic crossmatches were performed using pre- and posttransplant recipients' sera and donor lymphocytes and monocytes. Lymphocytes were isolated with Ficoll-Hypaque; monocytes by adherence to plastic Petri dishes. Of the 16 patients studied, only 1 had a positive pre- and posttransplant monocyte crossmatch. Crossmatches using recipients' T and B lymphocytes were uniformly negative, indicating the presence of anti-VEM antibodies in the absence of anti-HLA antibodies in this 1 patient. This patient rejected the transplant in the immediate posttransplant period. Of the remaining 15 patients, 4 lost their kidneys within 16 days posttransplant, whereas 11 have good graft function. We conclude that anti-VEM antibody occurs rarely pretransplant and is an unusual cause of immediate rejection in the living-related transplant situation. However, when anti-VEM antibody is identified, transplantation should be avoided because of the likelihood of immediate early rejection.