Using guinea-pig lung membranes and cloned human β2-receptor adrenergic receptors the effects of whole serum, plasma, purified immunoglobulins and cellular activation products on β2-adrenergic receptor ligand binding and function were investigated. Sera from 24 non-asthmatic subjects and 115 asthmatics in different clinical categories were studied. There were no significant differences between antagonist ([125I] cyanopindolol) inhibition mediated by serum, plasma or by purified IgG when the asthmatics were compared with non-asthmatics. There was also no inhibition of 10−6m isoproterenol stimulated cAMP release from L cells expressing human β2-adrenergic receptors, by plasma, DEAE purified IgG fractions from asthmatics and non-asthmatics, or by products of activated platelets or lymphocytes. Since we have no evidence that immunoglobulins from asthmatic subjects exert functional inhibition of human β2-adrenergic receptors we conlcude that autoantibodies to the β2-adrenergic receptors do not play an important functional role in the pathophysiology of asthma.