Abstract The activity of neurons in the caudate nucleus and reticular formation was recorded following intraperitoneal injection of the optical isomers of amphetamine. In general, d-amphetamine sulfate (2.0 mg/kg) produced an initial increase in firing rate of neurons in the caudate nucleus approximately 8—10 min following intraperitoneal injection, and a subsequent depression of firing rate which lasted for a period of time of from 70 to 120 min. Similar injections of l-amphetamine sulfate produced only a depression of activity in the caudate nucleus which was less marked and of lesser duration. Mephentermine sulfate (6.0 mg/kg), a peripheral sympathomimetic, did not produce these effects. Both d-amphetamine and l-amphetamine sulfate at the same dose produced an increase in firing rate of neurons in the reticular formation, although that produced by the l-isomer was less marked and of lesser duration. Mephentermine sulfate also produced an increase in reticular formation neuronal activity comparable to that produced by l-amphetamine sulfate. In some cases, neuronal activity was held for prolonged periods of time following injection. In the caudate nucleus, a rebound increase in firing rate was observed following the marked depression produced by both isomers of amphetamine. A rebound depression of activity was observed in the reticular formation following the initial increase in neuronal activity produced by these drugs. The results are discussed in terms of the known biochemical and behavioral effects of the stereoisomers of amphetamine.