The newer, second-generation H1-receptor antagonists have been shown to have potent antiallergic effects without inducing sleepiness. However, because traditional antihistamines may cause functional or cognitive impairment, the clinican still must consider warning patients about activities that could be hazardous. Because the effects of drugs on driving an automobile are difficult to measure directly, studies must use surrogate activities in a laboratory setting. Effects of antihistamines on the central nervous system are assessed with psychomotor tests, which are selected on the basis of their relativity to real-world activities, to develop a profile of mental processes that may be affected. This article reviews the psychomotor tests and study design used to characterize the intensity and duration of drug effects after single and multiple doses and in combination with other impairing agents such as ethanol. Several studies have been published that assess the effects of cetirizine, an H1-receptor blocker, on mental performance. In the study discussed here, diphenhydramine hydrochloride and hydroxyzine were used as positive controls to demonstrate that the period during which some traditional antihistamines impair performance is different than the period of reported drowsiness they induce. The results of this series of studies show that cetirizine induced minimal changes in mental performance tests and only following the highest (20 mg) dose studied.