1. Inside-out recordings from rat cortical fused nerve terminals indicate that the most common channel observed was a large conductance K+ (BK) channel with characteristics dissimilar to conventional cell body calcium-activated BK (BKCa) channels. 2. BK channels exhibit mode switching between low (mode 1) and high (mode 2) activity, an effect not influenced by membrane voltage. Increasing internal Ca2+ concentration increased time spent in mode 2 as did application of protein kinase A, an effect not mimicked by protein kinase C or protein kinase G. 3. Mode 1 activity was voltage independent although depolarization increased mode 2 channel activity. Global average channel activity was voltage and Ca2+ dependent. 4. Alkaline phosphatase treatment induced channel activity to reside permanently in mode 2, where activity was voltage and Ca2+ dependent but unaffected by protein kinases A, G or C. 5. Internal application of tetraethylammonium blocked BK channel activity in a manner identical to that reported for BKCa channels. 6. These results indicate that nerve terminal membranes have large conductance K+ channels with significant differences in gating kinetics and regulation of activity compared with BKCa channels of other neuronal preparations. The BK channel subtype may play a unique physiological role specific to the nerve terminal.