Rhabdomyolysis is an uncommon finding in the emergency department. However, the clinical implications of rhabdomyolysis are important, with a significant minority of patients developing acute renal failure and multiorgan failure. When present, the cause of elevated aminotransferases in the setting of rhabdomyolysis is often unclear. We sought to determine the incidence of abnormal aminotransferases (defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT)>40 U/L) in the setting of rhabdomyolysis and how the aminotransferases decrease relative to the creatine phosphokinase (CPK) concentration as rhabdomyolysis resolves. A retrospective chart review of 215 cases of rhabdomyolysis with CPK of >or=1,000 U/L was performed. The incidence of an abnormal AST in the setting of rhabdomyolysis was 93.1% (95% confidence interval, 88.7% to 95.8%). An abnormal ALT was much less common and found in 75.0% (95% confidence interval, 68.7% to 80.2%) of patients with a CPK of >or=1,000 U/L (p<0.0001). In only one instance was the ALT>40 U/L while the AST was <40 U/L. Furthermore, AST concentrations (and not ALT) fall in parallel with CPK during the first 6 days of hospitalization for patients with rhabdomyolysis. Aminotransferase abnormalities, particularly AST, are common in the setting of rhabdomyolysis. AST concentrations decrease in parallel to CPK, suggesting skeletal muscle may be a significant source of AST elevation in these patients.