Brain neurotransmitter content and uptake activity were assessed in the brains of 7-day-old rats 15 min after exposure to hypoxia (8% O2-92% N2) for 3 hr. Glutamate, dopamine and choline uptake were decreased in the striatum, hippocampus and frontal cortex of the hypoxic animals. Moreover, the content of glutamate, dopamine and serotonin as well as the acidic metabolites of the two biogenic amines increased in the same tissues. Acetylcholine content was decreased in all three brain regions as well. Treating the animals with GM1 ganglioside before the insult prevented all neurochemical changes in the hypoxic neonatal brain. GM1 also prevented an hypoxia-induced decrease in phorbol ester binding. Finally, GM1 ganglioside reduced the mortality rate resulting from the hypoxic insult. Our results along with those in the literature suggest that GM1 might be useful for combating the pathology associated with perinatal hypoxia.