A drug rechallenge proved chlorzoxazone to be hepatotoxic in a patient who had been treated with a combination of it and acetaminophen (Parafon Forte) for several months. Failure to demonstrate a toxic response to acetaminophen coupled with a dramatic response to a single dose of chlorzoxazone implicated chlorzoxazone as the hepatotoxic agent. A review of US Food and Drug Administration records and cases reported in the medical literature disclosed 23 cases of chlorzoxazone-associated hepatotoxic reactions occurring since 1970. These cases were examined in terms of age, duration of therapy, other confounding etiologic factors, and ultimate outcome. There were two deaths involving hepatic failure. Reports of adverse reactions among six commonly used analgesic-muscle relaxants in Sweden have indicated a low, but comparatively greater, incidence of hepatotoxic reactions associated with a chlorzoxazone-containing compound.