Orthotopic liver transplantation is today an accepted surgical procedure for patients with irreversible, end-stage liver disease. Between 1988 and 1993, seven patients (one patient twice) received liver grafts for end-stage liver disease at Howard University Hospital, Washington, DC. In conjunction with the transplant procedure, a total of 32 liver needle biopsy specimens were submitted to the pathology department. Almost half of all liver graft failures are attributed to acute, or in a lesser degree, to chronic rejection. The purpose of this study was to describe the ultrastructural findings in acute cellular rejection and to correlate the ultrastructure with the histology. The key ultrastructural features of acute cellular rejection were: a mixed cellular inflammatory infiltrate in the portal tract, bile duct damage by immunocytes with reduplication of the epithelial basement membrane, endotheliitis, and intramitochondrial crystalline inclusions. It was concluded that electron microscopic investigation significantly contributes to better understanding the immunopathologic mechanism underlying liver allograft rejection.