This study aimed to find a method to distinguish between bacterial and viral infection by measuring inflammatory markers in the early phase of the illness. We examined the activity of acute phase proteins, including C-reactive protein (CRP), serum amyloid A (SAA), and 2'-5'-oligoadenylate synthetase (2-5A synthetase), in sera obtained from children with bacterial and viral infections that were diagnosed by isolation of the pathogen or by positive serology. Increases in levels of CRP and SAA generally paralleled each other. In the acute stage of bacterial infections, CRP levels were moderately or highly increased and 2-5A synthetase levels were normal, whereas in viral infections, CRP levels were normal or slightly increased and 2-5A synthetase levels were increased. To better distinguish between bacterial and viral infection we used the ratio of CRP (mg/l) to 2-5A synthetase (pmol/dl) x10 as the differential index. The values for this index in bacterial infections ranged from 3.9 to 50, and were higher than the values in viral infections, which ranged from 0 to 0.9. We propose that the measurement of both CRP and 2-5A synthetase during the acute phase of illness (within 5 days of onset) is of value to determine whether the infection is caused by a bacteria or virus.