We report cases of amoxycillin- and flucloxacillin-induced liver damage associated with an acute vanishing bile duct syndrome. Ductopenia was present at the time of first liver biopsy, 3 weeks and 3 months after administration of the two drugs, respectively. Ductopenia apparently occurred as the primary lesion, with no evidence of accompanying portal tract inflammation. Subsequent biopsies showed a persistent paucity of ducts, accompanied by increasing features of chronic cholestasis. Biochemical dysfunction persists at 2 year's follow-up and late prognosis remains guarded.