Light microscopic, immunohistochemical and ultrastructural analysis of protocol before transplantation and after reperfusion biopsy specimens from 87 randomly selected patients was performed to assess the contribution of preservation and immunological injury to early graft failure. Most biopsy specimens were essentially normal by light microscopy before transplantation, and no particular feature could be relied on to predict function after transplantation. Ultrastructural examination of biopsy specimens before transplantation demonstrated preferential degeneration of sinusoidal lining cells, but no strict correlation was seen between ultrastructural sinusoidal integrity before transplantation and function after transplantation. The presence of zonal or severe focal necrosis and a severe neutrophilic exudate in biopsy specimens after reperfusion presaged a poor early postoperative course in most, but not all, patients. The presence of preformed lymphocytotoxic antibodies had no effect on the early clinical course, but was associated with Kupffer cell hypertrophy in needle biopsy specimens taken after transplantation. No definite evidence was seen of hyperacute rejection as a result of preformed lymphocytotoxic antibodies as detected in conventional assays. These findings suggest that preservation injury accounts for only a subset of grafts that fail to function after transplantation. Other perioperative or "recipient" factors may be of equal or greater importance in early graft dysfunction or failure.