In many physiological systems such as neurotransmitter release, smooth muscle relaxation and frequency tuning of auditory hair cells, large-conductance calcium-activated potassium (BK_Ca) channels create a connection between calcium signalling pathways and membrane excitability^,,,. BK_Ca channels are activated by voltage and by micromolar concentrations of intracellular calcium. Although it is possible to open BK_Ca channels in the absence of calcium^,,,,, calcium binding is essential for their activation under physiological conditions. In the presence of intracellular calcium, BK_Ca channels open at more negative membrane potentials^,,,,,. Many experiments investigating the molecular mechanism of calcium activation of the BK_Ca channel have focused on the large intracellular carboxy terminus, and much evidence supports the hypothesis that calcium-binding sites are located in this region of the channel. Here we show that BK_Ca channels that lack the whole intracellular C terminus retain wild-type calcium sensitivity. These results show that the intracellular C terminus, including the ‘calcium bowl’ and the RCK domain, is not necessary for the calcium-activated opening of these channels.