Intruction: Numerous pathophysiological conditions change during 24-hour periods. Histamine, the main mediator in allergic reactions, exerts a multiplicity of pathophysiological actions through binding to specific receptors on effector cells. Nocturnal exacerbation of symptoms occurs in many atopic diseases in which histamine is an important mediator. Nocturnal wheezing is a very common symptom of asthma. The aim of this study was to determine whether the binding of (fluorescein-labeled) histamine to cells participating in allergic-inflammatory processes (lymphocytes, neutrophils) and skin reactivity to histamine undergo circadian changes and to compare these phenomena in atopic asthmatic and healthy subjects. Materials and Methods: Blood samples were collected at 8 am, 2 pm, 8 pm, 2 am, and 8 am the next day. Histamine skin-prick tests were performed at the same times. Results: It was found that skin reactivity to histamine (wheal, erythema) in healthy subjects underwent significant circadian changes with acrophase at 8 am (wheal) or 8 pm (erythema), the lowest values being at night (2 am, p=0.017), in contrast to atopics, in whom the highest reactivity was found at night (2 am, p=0.002). Significant differences in the binding of fluorescein-labeled histamine between day (8 am?2 pm) and night (2 am) were observed for lymphocytes (p=0.006) and neutrophils (p=0.018). Conclusions: In the asthmatic group these changes were not significant. Circadian changes in both the binding of histamine by effector cells and skin reactivity to histamine were different in healthy and asthmatic subjects, and this may play a role in the pathomechanism, course, and chronopharmacotherapy of atopic diseases.