A retrospective review of all patients who received oxacillin i.v. in doses greater than 6 g/day was done. Eight patients in whom oxacillin-associated hepatitis developed were found and compared with a control group of 46 patients who received high-dose oxacillin and in whom oxacillin-associated hepatitis did not develop. The latent period to development of typical symptoms of hepatitis varied from 2-21 days. Laboratory abnormalities were compatible with anicteric hepatitis and reverted to normal after withdrawal of the drug. Oxacillin hepatitis probably represents a hypersensitivity reaction. Routine liver chemistries should be done regularly in all patients receiving high-dose i.v. oxacillin.