Objective To study the changes of the plasma tumor necrosis factor - α (TNF - α) and calcitonin- gene related peptide (CGRP) levels and their clinical implication in neonates with hypoxic - ischemic encephalopathy (HIE). Methods Dynamic variations of plasma TNF - α and CGRP levels were measured in 38 neonates with HIE and 18 normal neonates by radioimmunoassay. Results Plasma TNF - α and CGRP levels increased markedly in the acute stage of HIE and were (1. 12 ± 0. 42) ng/ml and (88. 92 ± 23. 16 ) ng/ml respectively, especially in the severe group [ (1. 28 ± 0. 41) ng/ml, (118. 12 ± 30. 25)ng/ml respactively) ] and the moderate moderate group (0. 95 ± 0. 30) ng/ml, (86. 49 ± 24. 36)ng/ml respectively]. TNF-- α and CGRP levels which were (0. 61 ± 0, 18) ng/ml and (68. 39 1±19. 32) ng/ml with HIE were reduced to normal levee in the convalescence stage. There was a positive correlation correlation between plasma TNF - α and CGRP levels in the acute stage of HIE. Conclusions TNF- α and CGRP might be involved in the pathophysiologic process of HIE. TNF- α may yield scathing effects of cerebral injury in the acute statge. CGRP may play a protective role in HIE.