Hepatic injury during long term dantrolene sodium therapy occurred in 19 of 1044 patients (1.8%) monitored for at least 60 days. Six had icteric hepatitis (0.6%) and 3 died (0.3%). After the marketing of the drug, an additional 31 cases of dantrolene-associated liver disease were available for analysis. Of these 16 had icteric hepatitis with a favorable outcome, whereas 11 died. The injury was mainly hepatocellular with a pattern of acute or subacute hepatic disease or chronic active hepatitis. Analysis of total of 50 cases showed a 28% case fatality rate. All the fatalities occurred in patients above 30 years of age and after at least 2 months of therapy, with 57% cases exposed for at least 6 months. Eleven of the 14 fatalities occurred in females (P is less than 0.05). No cases of hepatic disease occurred in patients exposed for less than 1 month or under the age of 10. The majority of adverse reactions (71%) occurred between 1 and 6 months of therapy. Daily dosage of 300 mg or more is associated with higher incidenceof hepatotoxic reactions and with the majority (85%) of the fatalities. The idiosyncratic hepatic injury does not appear to involve hypersensitivity to the drug. A careful assessment of the benefit-risk ratio in the therapeutic use of dantrolene sodium is proposed.