Thirty-five patients received 42 liver homografts between February 1984 and August 1985. One or more infections developed in 23 patients (66%) some time after transplantation. An average of 2.5 infections per infected patient occurred. Of 37 bacterial infections, two thirds were either bacteremias or localized intra-abdominal infections. The median onset was 29 days after operation. Thirteen viral infections were identified, with a median onset of 18 days after operation. Nine fungal infections, six disseminated and three localized, were identified, with a median onset of nine days after operation. Infection was the primary cause of death in five (14%) of 35 patients. Fatal infections were evenly distributed among bacterial (two), fungal (three), and viral (two) pathogens. Despite advances in surgical techniques and the use of cyclosporine, infection after orthotopic liver transplantation is a serious problem. Certain patients can be identified as high risks for infection and require an aggressive diagnostic workup followed by early institution of antimicrobial therapy.