This study investigated the safety and neuroprotective effect of moderate hypothermia in children with severe traumatic brain injury (TBI). Twenty-two children suffering from TBI were randomly divided into groups treated with moderate hypothermia (intracranial temperature of 34.5 +/- 0.2 degrees C, maintained for 72 h, n = 12) or normothermia (intracranial temperature of 38.0 +/- 0.5, n = 10). The cerebrospinal fluid levels of neuron-specific enolase (NSE), S-100, brain-specific creatine kinase (CK-BB), and intracranial pressure (ICP) levels were used to assess the protective effects. The variations in pH and electrolyte balance were also examined. The results indicated that the peak ICP level in the normothermia group (26.30 +/- 1.08 mm Hg) was reached 48 h after TBI. The ICP level in the moderate hypothermia group was lower than in the control group at every time point examined (p < 0.01). Furthermore, at 24, 48, and 72 h, the NSE, S-100, and CK-BB levels in the moderate hypothermia group were also lower than that of the normothermia group (p < 0.01). In the moderate hypothermia group, the pH and electrolyte balance at the end of the monitoring period were normal, but the heart rates were lower (p < 0.05). There were a total of three deaths (13.6%) in this study: one in the moderate hypothermia group (8.3%) and two in the normothermia group (20%). In conclusion, moderate hypothermia provided neuronal protection for children with severe TBI, and maintaining the intracranial temperature at 34.5 degrees C for 72 h was safe in this clinical setting.