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Background: An association between use of zidovudine and didanosine and a rare but life-threatening syndrome of hepatic steatosis, lactic acidosis, and myopathy has been reported., Objective: To describe the syndrome of hepatic steatosis, lactic acidosis, and myopathy in four patients taking stavudine., Design: Case series., Setting: A community hospital in Washington, D.C., and National Institutes of Health Clinical Center, Bethesda, Maryland., Patients: Two men and two women with HIV-1 infection who were taking stavudine presented with lactic acidosis and elevated levels of aminotransferases. All patients required intensive care., Measurements: Levels of lactic acid, alanine aminotransferase, aspartate aminotransferase, amylase, and lipase; computed tomography of the abdomen; liver biopsy (two patients); and muscle biopsy (two patients)., Results: Histologic findings consistent with mitochondrial injury confirmed the diagnosis of hepatic or muscle abnormality., Conclusion: Because hepatic steatosis may be life-threatening, physicians should consider it as a possible cause of elevated hepatic aminotransferase levels among patients taking stavudine.