The levels of natural soluble interleukin-4 receptor (shuIL-4R) were determined in the peripheral blood of 29 children with stable asthma, 10 children with asthma and acute respiratory infection, 11 healthy children with acute airway infection and 31 healthy controls. Healthy controls revealed the highest levels (median 1,082 pg/ml, range 524-1,900 pg/ml); which differed significantly from levels obtained with the blood of stable asthmatics (p < 0.01, median 658 pg/ml, range 329-1288 pg/ml), patients with asthma and acute respiratory infection (p < 0.01, median 663 pg/ml, range 0-1,250 pg/ml) and patients with respiratory infection alone (p < 0.01, median 674 pg/ml, range 466-1,110 pg/ml). In contrast, there was no significant difference in shuIL-4R content of cord blood obtained from newborns with a high or low risk of atopy. Additional analysis of interleukin-4 receptor (huIL-4R) on cultured lymphocytes from 13 stable asthmatic children and 14 healthy children indicated higher expression on CD4 cells (p < 0.05, median 2.2%, range 0.8-7.8%) compared to healthy controls (median 1.3%, range 0.7-3.3%). Therefore, diminished shuIL-4R concentrations in plasma may be related to inflammatory states but not specifically to atopy. The results support the notion that huIL-4R expressed on the cell surface may be regulated differently from the soluble form.