A severe and prolonged form of biopsy-proved cholestatic hepatitis occurred in a 45-year-old man who had received floxacillin for two weeks preceding the episode of drug-related cholestatic injury. Immunologic tests revealed evidence of in vitro sensitization to the drug as well as to the serum of a normal subject collected after ingestion of floxacillin. Floxacillin should be added to the list of drugs causing cholestatic hepatitis, most likely by an immunologic mechanism.