Sedation is regarded as a common side-effect of most H1-antihistamines. This view must be accepted, yet can hardly be assessed under treatment of allergic disorders. Since central sedative potency is hard to evaluate, different methods of measurement have been introduced in the four phases of clinical investigation. While tests of high complexity in early trials can detect true central effects, they seem to have the disadvantage of not taking into consideration the important interactions of drugs with the disorder. Therefore, we used a visual analog scale (VAS) as an instrument to demonstrate sedative effects in five clinical studies carried out between 1989 and 1994 with a total number of 1070 patients. Thereby, we could assess the result of the different components of the central interaction. In 1989, in a double-blind, placebo-controlled trial, we could show that the vigilance of patients suffering from seasonal allergic rhinitis increased significantly more under treatment with an antihistamine (mizolastine) than under placebo. From 1992 until 1994, we compared azelastine nasal spray either by the double-dummy technique with oral antihistamines (cetirizine, loratadine, and astemizole) or by the double-dummy or placebo-controlled design with monotherapy or combined therapy with azelastine tablets. A marked or statistically significant improvement of vigilance was found for all compounds (loratadine: P < 0.0001; cetirizine: P < 0.0254; and azelastine nasal spray: P < 0.1409 to P < 0.0001). Even when taking azelastine as oral application, patients, in spite of the warning, reported a similar increase in vigilance (P < 0.2628 to P < 0.0001). Finally, we assessed the range of physiologic vigilance using the same VAS in healthy volunteers. In conclusion, we could prove that in all trials the baseline values of vigilance of untreated symptomatic patients were far below physiologic condition and improved under treatment to the upper range of healthy persons. Therefore, any sedative properties of modern H1-antihistamines should not limit their therapeutic use, since the truly threatening sedation results from the disorder itself.