Phenylbutazone has been reported to produce several forms of hepatic injury. A clinical and histologic review of 23 well-substantiated cases in conjunction with review of 43 case reports in the literature was undertaken. Utilizing the histologic features and available clinical data, the injury was classified as moderate-marked hepatocellular injury, minor hepatocellular injury, and other injury. No sexual differences were noted. Most patients had used the drug for less than 6 weeks. Features of hypersensitivity were common. Granulomas on liver biopsy were seen mainly in association with clinical evidence of hypersensitivity nd with minor hepatocellular liver injury. The majority of deaths occurred in cases with significant hepatocellular injury or systemic vasculitis. Analysis of available data suggests that, although hypersensitivity appears to contribute to phenylbutazone-associated hepatic injury, the drug also appears to have intrinsic hepatotoxic potential. Speculation is offered regarding the relative role of these two mechanisms in the several forms of hepatic injury induced by phenylbutazone.