BACKGROUND: Although antihistamines are known for their sedative adverse effects, fexofenadine was previously shown to have stimulating effects. These stimulant effects were rather mild in magnitude and were only demonstrated in tasks with a high workload. AIM: The present study was set up to compare the magnitude of the stimulant effect of fexofenadine with those of 2 psychostimulants, modafinil and methylphenidate. METHOD: Sixteen healthy volunteers (5 males and 11 females; mean age, 21.8 years) participated in a 4-way, placebo-controlled, crossover study. The effects of fexofenadine (360 mg), modafinil (200 mg), methylphenidate (20 mg), and placebo were compared in a critical tracking, divided attention, motor impulsivity, and vigilance task. RESULTS: In this study, no significant stimulant effects of fexofenadine were found in any of the tasks. Modafinil only improved reaction time in the vigilance task, whereas methylphenidate improved performance in the divided attention and vigilance tasks. In addition, performance after methylphenidate treatment was also better than after fexofenadine in the divided attention and vigilance tasks. CONCLUSION: From the results, it can be concluded that the stimulating effects of methylphenidate are confirmed, whereas the stimulating effects of fexofenadine were not demonstrated in this study. It is evident that the stimulating effects of fexofenadine, which were apparent in previous studies, are not of the same magnitude as the effects of known psychostimulants such as methylphenidate.