Marked sleepiness occurs during typical night shift work hours and this reduced alertness is associated with marked performance deficits. The effect of caffeine (versus placebo) upon sleepiness at night was studied using objective measures of physiological sleep tendency and ability to sustain wakefulness. Both measures show caffeine to reduce sleepiness at a single dose roughly the equivalent of two to four cups of coffee. Despite impressive objective differences in alertness with caffeine, subjects did not consistently differentiate between drug conditions on subjective alertness assessments. The use of CNS stimulants to promote alertness during night shift hours should be considered, particularly for occupations for which alertness is critical.