Examination was made of the serum levels of interleukin 4 (IL-4), soluble Fc epsilon RII (sFc epsilon RII), and soluble interleukin 2 receptor (sIL-2R) in 77 adult patients with bronchial asthma. All the patients had mild to moderate asthma and their symptoms were well controlled. The results were compared with values for 75 control subjects to clarify the involvement of these factors in the pathogenesis of bronchial asthma. Serum sIL-2R was elevated in asthmatics compared with control subjects (459.0 +/- 30.4 U/ml vs 251.5 +/- 10.0 U/ml; p < 0.001). The IL-4 and sFc epsilon RII levels were also elevated beyond those in the controls (IL-4: 1.89 +/- 0.13 pg/ml vs 1.08 +/- 0.15 pg/ml; p < 0.001) (sFc epsilon RII: 313.2 +/- 18.8 U/ml vs 228.8 +/- 6.7 U/ml, p < 0.001). A weak but significant correlation was observed between sIL-2R and sFc epsilon RII (r = 0.46, p < 0.001). Correlation among other parameters was not found. The patients were divided into atopic and nonatopic groups, based on the presence or absence of positive reaction to skin prick tests using extracts of common aeroallergens and positive specific IgE against house dust mite (Dermatophagoides pteronyssinus [Dp]). Mean IL-4 in the atopic group, with positive skin reaction and > 0.7 kU/L specific IgE against Dp was significantly elevated compared with the nonatopic group (2.35 +/- 0.26 pg/ml vs 1.56 +/- 0.12 pg/ml; p < 0.005). Such differences could not be detected in sIL-2R, sFc epsilon RII levels among the two groups. No significant correlation could be found among IL-4, sFc epsilon RII, and total IgE level. The activation of T cells and B cells would thus appear essential to the pathogenesis of bronchial asthma and the hypothesis that atopic status is associated with the preferential activation of TH2 cells which selectively produce IL-4 could be supported. The regulatory mechanism of IgE synthesis would not appear to be the only responsible factor.