The mechanisms of HIV-1 neurotoxicity remain still undefined although the induction of signalling events and a modest inhibition of glutamate uptake induced by the envelope glycoprotein, gp120, have called attention to astrocytes. Here we demonstrate that the levels at which the viral glycoprotein affects glutamate homeostasis of astrocyte cultures are at least two: not only the inhibition of uptake, due to an effect at site(s) away from the transporters of the amino acid but also a slow stimulation of release. The combination of these two events accounts for a considerable steady increase of the extracellular concentration of the excitatory amino acid which could play an important role in the neurotoxicity often observed in AIDS patients.