The dose-effect and duration of action of several stimulants and tranquilizers were determined using motor and psychomotor performance tests with humans. Three doses of each of the following drugs were employed: placebo, caffeine, d-amphetamine, phenmetrazine, methyl phenidyl acetate, phenobarbital, chlorpromazine, meprobamate, and oxanamide. Phenmetrazine and methyl phenidyl acetate were also studied with additional tests designed to measure fatigue. Deanol and placebo groups were tested weekly for 8 weeks of daily administration crossing treatments at 4 weeks. The tranquilizers did not affect performance as measured by the tests employed, while all stimulants produced some improvements in all tests. Phenmetrazine and methyl phenidyl acetate were the most promising central stimulants tested. These were found to mitigate fatigue by elevation of the initial performance level and by decreasing the time-related decrement. The action of deanol was equivocal with some indication of an interaction between the drug and subject interest.