Vascular endothelial cells (ECs) are considered to be a primary target for injury in allograft rejection. However, the relationship between serum antibody activity to ECs and rejection episodes has not been examined extensively in renal transplantation. Twenty-two renal transplant recipients were included in this study. Serum antibody activity to vascular endothelial cells (AECA) was measured using a cellular enzyme-linked immunosorbent assay (ELISA) in which human umbilical vein endothelial cells (HUVEC) and human glomerular endothelial cells (HGEC) were preincubated with TNF-alpha used as target cells. Serum samples were obtained just before transplantation and once a week during the immediate 1-3-month post-transplantation period. There was a significant correlation between the presence of AECA against HGEC and rejection episodes (P < 0.05). Patients with multi-episodes of rejection showed significantly higher frequencies of AECA than patients with mono-episodic rejection (P < 0.0005). It should be noted that patients suffering from multi-episodes of rejection revealed higher AECA titres before transplantation. These findings imply that the HGEC-ELISA could be used as a prospective, informative test to identify patients with a higher risk of acute rejection in renal transplantation.