Between November 1990 and March 1992, 24 asymptomatic individuals in Chile with chronic hepatic fascioliasis confirmed by the presence of Fasciola hepatica eggs in feces were treated with a single oral dose of triclabendazole (10 mg/kg of body weight) after an overnight fast. Nineteen (79.2%) of 24 patients were egg-negative two months after treatment. Three of five cases with F. hepatica in feces after the first treatment were retreated and parasitologic cure was achieved. Tolerance to the drug was excellent; none of the patients had either secondary symptoms or important alterations in levels of aspartate and amino transferases, alkaline phosphatase, or bilirubin during or after treatment. Mild eosinophilia, present in 70% of the cases, persisted at least until 60 days after treatment. An enzyme-linked immunosorbent assay (ELISA) was highly effective in diagnosis and post-treatment monitoring. Before treatment, 20 (83.3%) of 24 confirmed cases had positive test results. The test results became negative by the second month of treatment in 40% of the cured cases. This percentage increased progressively, reaching 91.3% at 12 months after therapy. In the five cases in which treatment failed, the ELISA results remained positive until the end of the follow-up period (six months). In three of these cases who accepted a second round of therapy with triclabendazole six months after the first treatment, the ELISA results became negative in all three six months after parasitologic cure and remained negative until the end of the period. Due to its efficacy, excellent tolerance, and ease of administration (a single oral dose), triclabendazole appears to be the drug of choice for chronic human fascioliasis.