Hypothermia after hypoxia-ischaemia (HI) confounds the interpretation of the effects of neuroprotective drug intervention. The effect of 0.5 mg/kg of dizocilpine (MK-801) administered after HI on rectal temperature at 2-36 h and on brain damage 2 weeks after the insult was evaluated in the immature rat. In pups kept at an ambient temperature of 21 degrees C, MK-801 lowered the temperature by 1.1 degrees C and reduced the brain damage by 45%. In pups held at an ambient temperature of 33 degrees C, MK-801 treatment afforded a 34% reduction of brain damage without lowering the rectal temperature. In conclusion, the neuroprotection offered by MK-801 does not depend on systemic hypothermia in this model.