BACKGROUND GABAergic neurons synthesize and release gamma-aminobutyric acid, the predominant inhibitory neurotransmitter in the brain. Certain clinical signs of rabies and previous experimental studies have suggested that rabies viral infections affect the host GABAergic system. OBJECTIVE The effect of rabies virus infection on the expression of GABA was evaluated in neurons of the mouse cerebral cortex. METHODS Adult mice were inoculated by intramuscular injection with the standard strain of rabies (CVS virus). The animals were sacrificed in the terminal stage of the illness and perfused with 4% paraformaldehyde and 1% glutaraldehyde. Frontal sections were obtained in a Vibratome(R) and treated with appropriate immunohistochemical reactions for identifying the GABAergic neurons in the cerebral cortex. Counts and comparative quantitative analysis of the GABA+ neurons were compared in samples of infected and normal mice. RESULTS In the animals infected with rabies virus, the distribution pattern of cortical GABAergic neurons was not changed, but their number diminished significantly. The mean value of GABA+ cells number in 1 microm2 of cerebral cortex was 293+/-32 in normal samples and 209+/-13 in infected samples. Despite the loss in GABA+ cell number, the average size of GABA+ cells per unit increased from 104+/-8 microm2 in normal mice to 122+/-10 microm2 in infected mice because the cell loss consisted more frequently of smaller neurons. Nevertheless, the rank of GABA+ cell sizes in infected samples was similar to normal samples. CONCLUSIONS This evidence supported the hypothesis that GABA is involved in rabies pathology.