Background: The "vascular depression" hypothesis has sought to explain differences in etiology between early and late life depression, and has been reinforced by recent imaging and morphometric studies. Gamma-aminobutyric acid (GABA) is thought to play a major role in the neurobiology of depression. However, it is unclear whether there is an effect on GABA neuronal subpopulations in an elderly depressed cohort. This study therefore examined immunohistochemically two calcium-binding proteins, calretinin and parvalbumin, which have been demonstrated to bind to two distinct GABAergic interneuron subpopulations, within the dorsolateral prefrontal cortex (DLPFC) of elderly depressed patients, against age-matched controls. Methods: Post-mortem tissue was obtained from nine controls and 11 depressed patients for the parvalbumin study and seven controls and 14 depressed patients in the calretinin study, and the mean percentage per area of immunohistochemical staining of the two antibodies was measured in individual layers and across the whole of the DLPFC. Results: The study found a reduction in parvalbumin immunostaining in layer 6 (p = 0.05) of the DLFPC in elderly depressed patients. However, no significant changes were found in parvalbumin or calretinin immunostaining in the any other layer of the DLPFC in elderly depressed patients. Conclusion: The study does not suggest any change in GABA interneuron subpopulations, though significant reductions in layer 6 may represent subtle disturbance in GABA parvalbumin-expressing interneuron and glumatatergic pyramidal projection neuron regulation in late-life depression.