Recurrent HCV infection is almost universal after LT. Amantadine (Am) has been used in immunocompetent HCV patient with chronic hepatitis. We investigated the effectiveness and safety of Am-based antiviral treatment in HCV LT patients with biopsy-proven recurrent disease. 12 patients (55 yrs, 9 males) with a 1-4 yrs follow up were enrolled. Inclusion criteria were: 1) detectable serum HCV RNA; 2) evidence of disease recurrence with hepatic fibrosis. Basal Ishak's grading and staging score were 2.1 and 5.1, respectively. Exclusion criteria were cirrhosis and concomitant morbidities. Am was given orally (100 mg/die) during three months. Clinical and biochemical data were recorded monthly, whereas HCV RNA before and after the study period. 8 (67%) pts completed the 3-month treatment without dose-adjustment. Am was reduced to 100 mg/die in 3 pts and withdrawn in one, due to side effects (SE). These included insomnia (7), tremor (4), headache (2), asthenia (2), dermatitis, diarrhoea and increased function (1). SE was more pronounced in pts with abnormal renal function. HCV RNA decreased in 3 pts, increased in 3, while remained stable in the remainders. Liver function tests did not improve during the study period. Short-term Am monotherapy is ineffective in HCV LT patients also entailing significant SE.