During the oestrous cycle, falling progesterone levels during late dioestrus are associated with increased expression of α4, β1 and δ GABA_A receptor subunits on neurones in the periaqueductal grey matter (PAG) [1]. We have carried out experiments to determine which cell type/s show plasticity of receptor expression and the functional consequences in terms of neuronal excitability. Dual immuno-labelling for glutamic acid decarboxylase (GAD) and α4, β1 or δ GABA_A receptor subunits (antibodies GAD67, Chemicon and sc-7355, sc-7361 and sc-7369, Santa Cruz Biotechnology respectively) was performed on sections of midbrain from urethane-anaesthetised (0.5ml 100g^-1 i.p.) adult female Wistar rats. In proestrus (n=5), oestrus (n=5) and early dioestrus (n=5), most of the α4, β1 and δ-subunit positive cells (91%, 90% and 91% respectively) showed co-localisation with GAD. In late dioestrus (n=5), when the numbers of α4, β1 or δ GABA_A receptor subunit positive cells are significantly increased [1], the proportion remained similar (84%, 85%, 81% respectively), indicating that the increased expression occurred predominantly on GABAergic neurones. In functional experiments, extracellular recordings from presumed output neurones in the PAG of female urethane-anaesthetised rats (0.5ml 100g^-1 i.p.) were made using multibarrelled micropipettes filled with 4M NaCl, 0.1M D,L-homocysteic acid (DLH), 0.25M GABA, 0.2M bicuculline methiodide (BIC) and 1% pontamine blue in 0.5M sodium acetate. Most cells were quiescent. A basal level of firing (5.6±0.3Hz, mean±S.E.M) was therefore induced with continuous application of DLH. Against this, application of BIC (0-30nA) produced a graded increase in firing rate indicating the presence of tonic GABAergic inhibition. In oestrous and late dioestrus, when progesterone levels are falling rapidly [2], the maximum firing rate attained in the presence of 30nA BIC (40.1±9.0Hz, n=5 and 30.4±4.2Hz, n=12 respectively) was significantly greater than in proestrus and early dioestrus (19.6±1.9Hz, n=8 and 18.0±1.8Hz, n=8 respectively, p<0.05 Student’s t-test). We suggest that in late dioestrus, new α4β1δ receptors are expressed on GABAergic neurones and lead to a decrease in their excitability. Thus output neurones in the PAG would be expected to be disinhibited due to a reduction in inhibitory GABAergic tone. Hence BIC would become more effective in blocking the residual tonic inhibition. A similar event may occur during oestrus.