Using a continuous perfusion system, synaptosomes prepared from rat brain released [ 3H]norepinephrine in a Ca 2+-dependent manner when pulse depolarized by briefly elevating external potassium concentrations. Tetrodotoxin (10 −7M), a sodium channel blocker, inhibited 48% of this pulsed release, and D595 (10 −5M), a phenethylamine-type calcium channel blocker, inhibited 21%. In combination, these two specific ion channel antagonists appear to function independently of each other in an additive fashion. Addition of deltamethrin to this preparation resulted in an enhanced release of [ 3H]norepinephrine which occurred in a biphasic fashion. At 10 −7M, deltamethrin produced a 42% enhancement in the first or initial peak of [ 3H]norepinephrine release and a 100% enhancement in the second or tailing peak. Addition of deltamethrin to tetrodotoxin-pretreated synaptosomes resulted in a net 37% enhancement of the initial peak release and a net increase of 277% in the tailing peak. Addition of deltamethrin to D595-pretreated synaptosomes produced no significant effect on enhanced [ 3H]norepinephrine release from either peak. Since tetrodotoxin is a specific sodium channel blocker, deltamethrin may be enhancing [ 3H]norepinephrine release by increasing the uptake of Ca 2 via other voltage-gated channels (e.g. calcium) or exchange mechanisms in addition to its action at voltage-gated sodium channels. To determine whether deltamethrin may also have an effect on intraterminal Ca 2+ homeostasis, external Ca 2+ was replaced with Ba 2+ and synaptosomes were depolarized with pentylenetetrazole (PTZ). At 10 −5 M, deltamethrin produced a 66% increase in neurotransmitter release over that produced by PTZ alone. An estimated ec 50 value of deltamethrin for PTZ-induced release was calculated to be 2.4 × 10 −10M.