The daytime sleepiness potentially associated with antihistamines was evaluated by the multiple sleep latency test (MSLT) in a study comparing terfenadine with placebo. According to a double-blind, randomized, cross-over design, 12 healthy men were given either 120 mg terfenadine or placebo once daily in the morning, for 3 consecutive days with a 5-day interval. EEG-polygraphic recordings were made each study day at 9:30 and 11:30 a.m., and 1:30, 3:30, and 5:30 p.m., and the tendency to fall asleep was measured. All mean stage-1 sleep latencies throughout the study failed to show any significant difference between terfenadine and placebo. Accordingly, psychomotor performance assessed by visual and auditory reaction time did not change after treatment. The results of this study confirmed that terfenadine does not induce daytime sleepiness as objectively measured by MSLT.