Single channel recordings of large conductance Ca2+-activated K+ (BKCa) channels were made from neurones isolated from rat motor cortex. Application of levcromakalim, pinacidil or diazoxide had no effect on BKCa channel activity in excised patches. In contrast, NS 1619 (1-(2′-hydroxy-5′-trifluoromethylphenyl)-5-trifluoromethyl-2(3H)benzimidazalone) induced concentration-dependent activation of BKCa channels with a calculated EC50 of 32 μM. The NS 1619-induced activity was dependent on the presence of free Ca2+ at the intracellular surface, but was not associated with a change in channel voltage sensitivity. Niflumic acid had no effect on BKCa activity per se but prevented NS 1619-mediated activation.