Interleukin (IL)-4, IL-5 and interferon (IFN)-gamma are thought to play an important role in chronic airway inflammation in asthmatic subjects. Increased airways responsiveness and nocturnal airway obstruction are important clinical manifestations of asthma. The aim of this study was to investigate whether IL-4, IL-5 and IFN-gamma values are elevated in atopic asthma and correlate with its clinical manifestations. Serum IL-4, IL-5 and IFN-gamma levels of 17 atopic asthmatics and eight nonatopic healthy subjects were determined at 16:00 and 04:00 h by a chemiluminescence enzyme-linked immunosorbent assay (ELISA) method. The clinical manifestation of asthma was determined by assessment of the degree of airway obstruction, airways responsiveness to methacholine and severity of nocturnal airway obstruction, defined as the mean circadian (16:00-04:00 h) peak expiratory flow (PEF) variation. Serum IL-4, IL-5 and IFN-gamma levels were significantly higher in asthmatic subjects as compared to healthy controls, both at 16:00 and 04:00 h. In asthmatic subjects serum IFN-gamma at both time points correlated significantly with the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20,meth) (rho= - 0.55) and with the mean 16:00-04:00 h PEF variation (rho = 0.53). In contrast, no relationship was found between the levels of IL-4 and IL-5 and the parameters of clinical manifestation of asthma. The results suggest that the serum interferon-gamma level is a reflection of the severity of airway inflammation in atopic asthma. More studies are needed to detect the cellular sources and to clarify the exact roles of interferon-gamma and other pro-inflammatory cytokines in asthma.