Acute hepatocellular injury, whether due to viral hepatitis, hepatic ischemia, or drug hepatotoxicity, results in elevated levels of serum aminotransferases (AST and ALT). Serum lactate dehydrogenase (LD) is reported to be markedly elevated in ischemic hepatitis. Thus, comparisons of the degree of elevation of serum levels of LD, ALT, and AST may be helpful in the differential diagnosis of acute liver injury. To study this, we reviewed serum enzyme patterns early in the course of acute liver injury in patients with acute viral hepatitis A and B (n = 51), ischemic hepatitis (n = 20), and acetaminophen injury (n = 26). All patients had serum ALT and/or AST at least five times the upper limit of normal. For a given ALT and AST level, LD was higher in ischemic hepatitis and acetaminophen injury than in viral hepatitis. The mean ALT/LD ratio for acute viral hepatitis was 4.65, for ischemic hepatitis 0.87, and for acetaminophen injury 1.46. Mean ALT/LD ratio for viral hepatitis was significantly higher (p < 0.0001) than for the other two groups combined. An ALT/LD ratio of 1.5 differentiated acute viral hepatitis from ischemic hepatitis and acetaminophen injury with a sensitivity of 94% and a specificity of 84%.