Presynaptic and postsynaptic actions of dextroamphetamine (DEX) were studied on dopamine (DA) sensitive neurons of the subesophageal ganglion of the garden snail Helix aspersa utilizing standard microelectrode techniques. Dextroamphetamine (5.5 × 10-7-10-4 M) produced effects on DA-sensitive neurons similar to that caused by DA (5.5 × 10-7-10-4 M). On cells excited by DA, surfused DEX (5.5 × 10-7 M) caused an excitation that could be blocked by chlorpromazine (0.5-1 × 10-6 M) or haloperidol (0.5-1 × 10-6 M). Elevating the extracellular Mg2+ from 4 to 20 mM reduced the depolarization caused by DEX from 11 to 2.5 mV without affecting the response to DA. The response remaining is attributed to a direct response to DEX on DA receptors. Surfused DEX caused an inhibition of cells inhibited by DA. Both DA and DEX effects were selectively blocked by dihydroergotamine (0.5-1 × 10-6 M). Elevating the [Mg2+] decreased the hyperpolarization caused by DEX from 11 to 3 mV without affecting the DA response. The effect of elevated magnesium in decreasing responses to surfused DEX suggests that the primary action of DEX is at the nerve terminal to cause DA release. Iontophoretic application of DEX caused minimal excitation or inhibition of DA neurons. This is attributed to the fact that DA receptors at the site of drug application are not associated with synaptic innervation. The response obtained with iontophoretically applied DEX suggest a weak direct action on DA receptors.