The loss of hepatic allografts to the rejection processes is now relatively rare, and the reduction of adverse effects related to immunosuppressive therapy is becoming more important as patients survive longer after transplantation. We therefore investigated the response to a contact neoantigen before liver transplantation as a predictor of acute rejection after transplantation. Forty-one patients with chronic liver disease were sensitized with 0.1% diphenylcyclopropenone while on the waiting list for orthotopic liver transplantation. Fourteen days later an elicitation reaction was performed with 5 different concentrations of diphenylcyclopropenone. Nineteen responded to diphenylcyclopropenone (score range, 1-9). Twenty-two patients had no response. Three patients died before transplantation (all nonresponders). Twelve (63%) of 19 responders had treatment for acute rejection compared with 1 of 19 nonresponders (P < .0001). In addition univariate analysis revealed recipient age, donor age, Child-Pugh class, and immunosuppressive agent to be associated with acute rejection. On multivariate analysis only skin test response was a significant predictor of acute rejection (P = .02). All nonresponders had no or only mild rejection on biopsy, but 12 of 19 responders had moderate or severe acute rejection on biopsy. All patients requiring additional therapy to a single course of corticosteroids for acute rejection had skin test scores greater than 1. We concluded that patients who do not respond to diphenylcyclopropenone sensitization before transplantation develop at most mild acute rejection and that skin test scores identify patients with troublesome rejection. Evaluation of skin test responses to a contact neoantigen may facilitate tailoring of immunosuppressive therapy.