We describe a case of severe cholestatic liver disease, which persisted for 7 years, and was probably induced by flucloxacillin. We also report a survey of 77 liver reactions which were probably or possibly induced by penicillinase-resistant penicillins and spontaneously reported to the Swedish Adverse Drug Reactions Advisory Committee. The reactions were usually cholestatic with a tendency to a protracted course. There is some evidence for an immunoallergic idiosyncratic reaction. The incidence of reported liver reactions was estimated from sales data to be 1.6-2.9 per million DDD (defined daily doses) or, for flucloxacillin 1:11,000-1:30,000 prescriptions. Female sex, age and high daily doses seemed to be associated with higher risk of liver reactions from flucloxacillin.