Sulindac (Clinoril), an anti-inflammatory drug increasingly used in Australia for the treatment of rheumatological conditions, is unpredictably associated with a cholestatic hepatitis. We present three cases of sulindac hepatitis. The first case exemplifies acute sulindac hepatitis, the second, continuously exposed to sulindac for 18 months, had chronic sulindac hepatotoxicity, and in the third case, the long-term histological outcome after cessation of sulindac is described. The clinical, biochemical, and histopathological characteristics are those of a cholestatic hepatitis which resolves on withdrawal of the drug. We report marked anisonucleosis with cytoplasmic invaginations into the nucleus and binuclearity of hepatocytes as additional histological features of sulindac hepatitis. There is no evidence that sulindac hepatitis progresses to irreversible structural liver damage, although nuclear changes may persist for up to two months after cessation of the drug. The clinical and biochemical features of all reported cases of sulindac hepatitis are summarised.