Radioligand binding of the opioid receptor subtype selective ligands, [3H][D-Ala2,N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) (mu), [3H][D-Pen2,D-Pen5]-enkephalin (DPDPE) (delta) and [3H]U-69,593 (kappa), to rat brain particulate preparations was virtually unaffected by 1-100 microM glibenclamide (Glib) or tetraethylammonium bromide (TEA). These results argue against opioid receptor antagonism by Glib or TEA and support the hypothesis that antagonism of opioid-induced antinociception by Glib or TEA occurs at the level of K+ (possibly ATP-sensitive KATP) channels.