BACKGROUND: Differential diagnosis between a generalized tonic-clonic seizure and syncope may be difficult due to similar clinical features. The need for a biological marker to distinguish a seizure from syncope has been emphasized from past studies. Transient hyperammonemia could be an indicator of recent convulsive seizure. The purpose of this study is to review the use of plasma ammonia level in the differential diagnosis of seizure and syncope. METHODS: Adult patients who were admitted to the Department of Neurology at Gangnam Severance Hospital with final diagnosis of a generalized tonic-clonic seizure or syncope were eligible for this study. Plasma ammonia levels were checked within 8 hr after an insult. RESULTS: Among the patients with a loss of consciousness who underwent analysis of plasma ammonia level, diagnoses were made with a seizure (n=65) and syncope (n=38). The seizure group had 70.29+/-70.86 micromol/L and the syncope group had 28.37+/-10.27 micromol/L of ammonia level, respectively. The seizure group presented with a significantly increased plasma ammonia (p<0.05) compared to the syncope group. The cut-off value with the reliable diagnostic level was defined as 36 micromol/L (=61.308 microg/dL) with a sensitivity of 0.65 and specificity of 0.80 by receiver operating characteristic (ROC) curve analysis. CONCLUSIONS: Plasma ammonia measurement during acute post-ictal period may be a useful test for the identification and the differential diagnosis of seizures and syncope.