Background Acute vascular rejection (AVR) is characterized by vascular injury and systolic graft dysfunction and is often associated with elevated panel reactive antibodies (PRAs) to HLA antigens.Plasmapheresis has been shown to improve the otherwise poor prognosis of AVR, but its use is often complicated and limited by hypotension.Methods and Results In three cardiac transplant recipients with severe hemodynamic compromise during AVR, refractory to standard therapy, extracorporeal immunoadsorption was performed using a protein A column.Plasma was removed at 10 to 20 cm3/min, passed through the column, and reinfused. All three patients had negative pretransplant PRAs. PRA rose before or during AVR and became negative in all three patients following immunoadsorption. Time course and number of treatments required to decrease PRA to <5% varied. Concomitant with a decrease in PRA, histological findings and ventricular function improved and normalized. Ejection fraction rose from 23+-2 to 56+-8% and shortening fraction from 14+-7 to 36+-7%, P<.05 (both). One patient died from infection 2 months after resolution of AVR; the other two patients are alive 25 and 31 months after AVR with normal left ventricular function and coronary arteries. In both, since initial immunoadsorption course, PRA has remained negative and no rejection has occurred. In two patients, a circulating donor-specific or donor-related anti-HLA class I antibody was identified and removed by protein A column.Conclusions Our preliminary data suggest that (1) immunoadsorption is effective in removing circulating immunoglobulins and is well tolerated; (2) AVR is preceded by or associated with circulating antibodies against HLA class I antigens; (3) their removal is temporarily associated with recovery of graft function and normalization of biopsy; and (4) anti-HLA class I antibodies can mediate vascular injury if they appear in the post-transplant period. (Circulation. 1994;90(part 2):II-70-II-73.)