GABA-modulin, an endogenous membrane protein, which inhibits non competitively 3H-GABA binding to synaptic plasma membranes, has been isolated and purified to homogeneity using acidic extraction followed by Sephadex column purification and HPLC. GABA-modulin is a peptide of 18,000 MW which inhibits the binding of 3H-GABA and the GABA-induced stimulation of 3H-diazepam binding to synaptic membranes. The role of GABA-modulin in the control of GABA receptor system function is presently being investigated.