The influence of human leukocyte antigen (HLA) on acute liver allograft rejection was investigated in 48 adult patients. The diagnosis of rejection was always based on the full triad of histological findings, clinical signs, and the required antirejection treatment. Sixty-two percent of the patients closely observed for 6 months postoperatively revealed acute rejection within the first 3 weeks, mostly on days 7-11. HLA compatibility was not observed to have any significant influence on the incidence of acute rejection. However, different histological and clinical features were revealed in conjunction with DR compatibility. Patients without DR compatibility showed a type of rejection with fever and increase of bilirubin, frequently associated with cholestasis and cholangitis, which sometimes persisted for weeks. Patients with 1 DR compatibility showed a predominant increase of transaminases, which was never associated with cholangitis. The conjunction of different DR compatibilities and various clinical signs may indicate possible pathways from immunological assault to the clinical appearance of acute rejection. A knowledge of a patient's individual compatibility and an expectation of certain rejection patterns may lead to earlier and more reliable diagnosis and treatment.