This study reports the results on psychomotor functioning of D- and L-fenfluramine alone, and in combination with D-amphetamine, in a placebo-controlled trial on 12 normal male volunteers, in order to investigate their CNS activity in humans. The major findings were that D-amphetamine increased alertness, L-fenfluramine increased unhappiness whilst D-fenfluramine decreased hunger and increased the critical flicker fusion threshold. D-Amphetamine in combination with D-fenfluramine increased the critical flicker fusion threshold and in combination with L-fenfluramine the alerting action was diminished. The differing actions of the fenfluramine isomers and their interactions with D-amphetamine suggest that D-fenfluramine is predominantly serotonergic in its activity, whereas L-fenfluramine may be causing dopamine blockade, reducing certain actions of amphetamine possibly mediated by dopamine receptors. The significance of these results in relationship to the psychopharmacology of serotonin, dopamine, and noradrenaline is discussed.