In the present report, we investigated the potential involvement of imidazoline I 1 and I 2 binding sites in the inhibition of the Ca 2 + -activated K + channel (Gardos channel) by clotrimazole in human red cells. Ca 2 + -activated 8 6 Rb influx was inhibited by clotrimazole and efaroxan but not by the imidazoline binding site ligands clonidine, moxonidine, cirazoline and idazoxan (100 μM). Binding studies with [ 3 H]idazoxan and [ 3 H]p-aminoclonidine did not reveal the expression of I 1 and I 2 binding sites in erythrocytes. These data indicate that the effects of clotrimazole and efaroxan on the erythrocyte Ca 2 + -activated K + channel may be mediated by a non-I 1 2 binding site.