OBJECTIVE: To explore the mechanism of ameliorative effects of the nerve growth factor (NGF) on newborn rats with hypoxic ischemic brain damage (HIBD). METHODS: NGF dosage (0.1 μg/kg and 0.3 μg/kg) was administrated intraperitoneally to the rat pups 30 minutes before and immediately following the hypoxic exposure. The percentage of brain water content was determined according to the formula: (wet weight dry weight)/wet weight×100=% water content. Brain tissue calcium concentration was measured with atomic absorption spectroscopy. Monoamine neurotransmitter concentration in the rat brain was measured using high performance liquid chromatography with electrochemical detector (HPLCECD). RESULTS: Brain water content, calcium conentration and monoamine neurotransmitters (except DOPAC) concentration increased significantly after hypoxicischemic insult in the ipsilateral hemisphere of the HIBD group compared with the contralateral hemisphere and/or control group: water contents=(91.44±2.21)% vs (82.99±6.53)% (P<0.05) and (91.44±2.21)% vs (87.22±1.13)% (P<0.05) respectively; calcium concentration=(255.24±122.6) μmol/g dry weight vs (44.12±13.54) μmol/g dry weight (P<0.01) and (255.24±122.6) μmol/g dry weight vs (42.68±4.35) μmol/g dry weight (P<0.01), respectively. There were significant discreases in water content, calcium concentration and monoamine neurotransmitters (except DOPAC) concentration in the 0.1 μg/kg and 0.3 μg/kg NGFtreated HIBD group (compared with untreated HIBD group): water contents=(86.86±0.86)% and (87.45±0.3)%, respectively; calcium concentration=(44.34±3.10) μmol/g dry weight and (42.03±14.99) μmol/g dry weight, respectively. No differene was found between the NGF group and control group. CONCLUSIONS: Water content, calcium concentration and monoamine neurotransmitters may be involved, alone or interactively, in the pathophysiologic process of HIBD. NGF has ameliorative effects on newborn rats with HIBD, possibly through maintaining calcium homeostasis, ameliorating brain edema and attenuating or inhibiting the neurotoxic effects of monoamine neurotransmitters.