The functional significance of soluble-HLA Class I (S-HLA-I) and Class II(S-HLA-II) antigens is unclear. They are thought to have immunomodulatory properties. We, therefore, examined the expression of S-HLA-I and S-HLA-II in sera from patients with bronchial asthma according to their racial background. Using a solid phase ELISA, the levels of S-HLA-I and S-HLA-II were measured in 11 African-American and 13 Caucasian patients with bronchial asthma, as well as in healthy individuals (n = 66 African-Americans and n = 82 Caucasians). The levels of S-HLA-I in asthmatic patients (mean = 363 ng/ml in African-Americans and mean = 287 ng/ml in Caucasians) were close to those found in respective racial population of normal controls (mean = 337 ng/ml in African-Americans and mean = 241 ng/ml in normal Caucasians). In contrast, the concentration of S-HLA-II was statistically increased (p = 0.003) in patients with bronchial asthma. No statistical difference (p = 0.5) in S-HLA-II concentrations was demonstrated between African-American and Caucasian asthmatic patients. Based on the proposed immunomodulatory function of both S-HLA-I and S-HLA-II the increased levels of S-HLA-II identified in patients with bronchial asthma may contribute to the pathophysiology of this disease. Further studies with the presence of selected clinical parameters in multiple ethnic groups will provide more details on the relationship between S-HLA and bronchial asthma.