['Inflammation and inflammatory markers play an important role in acute ischemic stroke (AIS). In an earlier study, we discovered a 120-kDa protein that was highly expressed in healthy participants, but either was not expressed or was barely expressed in AIS patients. The purpose of the present work was to isolate, characterize, and evaluate this 120-kDa protein in blood samples of AIS patients. In addition, we investigated how the identified protein compared with protein S-100betabeta, neuron-specific enolase (NSE), and cytokine interleukins IL-2 and IL-10.', 'The 120-kDa protein band was analyzed via LC-MS/MS analysis. Then, the 120-kDa protein was evaluated using an enzyme-linked immunosorbant assay in serum samples from AIS patients, which were collected 0, 24, 48, 72 and 144 h after admission.', 'The amino acid sequence of an internal fragment identified the 120-kDa protein as inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4). The ITIH4 protein was completely absent in AIS patients as compared to those in the control group, and serum levels returned to normal in AIS patients as their condition improved. Expression of S-100 betabeta, NSE, IL-2, and IL-10 were highly correlated with ITIH4 expression.'] Is inter-alpha-trypsin inhibitor heavy chain 4 a novel marker of acute ischemic stroke?