The concentrations of L-aspartate, L-glutamate, L-serine, glycine and gamma-aminobutyric acid (GABA) were determined in repeated samples of ventricular CSF from five patients with severe closed head injury. The values were compared with those obtained from five subjects undergoing surgical treatment for intractable depression. In the head-injured patients, the concentrations of aspartate, glutamate and glycine were 2- to 8-fold higher and the concentration of GABA 56- to 317-fold higher than control values; the concentration of serine was unaffected. Spearman correlation analysis indicated that the concentration of glutamate significantly increased after injury (Rs = 0.60, p < 0.0001, n = 42), reaching an average concentration of about 7 microM 3 days after the injury. This is probably sufficient to cause further excitotoxicity, which suggests the use of excitatory amino acid receptor antagonists as a treatment following severe head injury may require prolonged administration for maximum therapeutic benefit.