The ability of sera from 11 patients with rheumatoid arthritis (RA) complicated by leukocytoclastic vasculitis (RV) to induce injury to cultured monolayers of human umbilical vein endothelial cells (HEC) was investigated. Injury was assessed in vitro using assays of cell lysis and cell detachment. Sera from patients with RV produced neither direct injury to HEC monolayers nor indirect injury when cocultured with HEC and normal peripheral blood polymorphonuclear cells (PMN). However, immune complexes (Icx) isolated from these sera induced nonlytic PMN-mediated HEC detachment. The inhibitory effect of serum on PMN-mediated HEC detachment induced by Icx could be attributed both to a different response of PMN to Icx present in serum compared to isolated Icx and to the presence of protease inhibitors in serum. The results of this study show that sera from patients with RV do not contain factors that can injure HEC directly and provide further support for the hypothesis that Icx and PMN play important roles in the pathogenesis of immune vascular injury.