Eighty-five patients undergoing single lung transplantation have been studied to determine the presence of anti-epithelial cell antibodies (AECA) prior to transplantation using the human lung carcinoma epithelial cell line A549 in a microcytotoxicity assay. In addition, 29 healthy volunteers were also assayed for the presence of AECA. Twenty-seven of the 85 recipients exhibited AECA prior to transplantation compared to none of the 29 control subjects (p = 0.0001). Actuarial graft survival at 1 year was 78% for the AECA negative group compared to 56% for AECA positive recipients (p = 0.01). No correlation was seen between the presence of AECA and graft rejection as determined by transbronchial biopsy. However, there was an association between AECA and post-transplant infection (p = NS) where 16 (64%) of the AECA positive recipients had postoperative infection episodes compared to 25 (47%) of the negative recipients. Sodium dodecylsulphate polyacrylamide gel electrophoresis and Western blotting was also performed for 68 of the recipients and antibody reactivity was detected in 22 patients compared to 26 patients exhibiting AECA detectable by microcytotoxicity. The presence of AECA demonstrable by Western blotting did not correlate with graft survival, rejection or infection. In conclusion, AECA detectable prior to single lung transplantation are associated with a decrease in graft survival and with postoperative infections.