Although one of the histamine-2 (H2) receptor antagonists, oxmetidine, has been shown to be intrinsically hepatotoxic, overt liver injury attributable to the commonly used analogues such as ranitidine is rare, given the millions of patients who have received this medication. However, isolated cases of hepatitis associated with ranitidine have been reported in the literature since the early 1980s when this drug was first introduced. We report a case of cholestatic hepatitis associated with ranitidine use. Liver biopsy showed diffuse panacinar canalicular cholestasis and cholestatic rosettes in zone 3. The clinical syndrome and the laboratory abnormalities resolved completely after discontinuation of the drug. There have been a few other published reports of ranitidine associated acute cholestatic hepatitis, and in this case ranitidine was temporally related to the onset of symptoms and liver enzyme abnormalities. With recent over-the-counter (OTC) availability of the H2 receptor antagonists and the increasing use of these drugs in the general population, physicians need to be aware of this rare but potentially serious side effect of ranitidine.