Abnormal autonomic nervous system responsiveness may contribute to the pathogenesis of asthma and other allergic diseases. Therefore, we measured alpha- and beta-adrenergic and cholinergic responsiveness in allergic subjects. Allergic asthmatic subjects had an abnormal adrenergic (alpha = hyperresponsive; beta = hyporesponsive) and cholinergic (hyperresponsive) profile. However, subjects with allergic rhinitis and preallergic subjects (those with positive allergen skin tests without any disease manifestation) had equivalent beta-adrenergic and cholinergic abnormalities. Thus, all allergic subjects showed abnormal beta-adrenergic hyporeactivity and cholinergic hypersensitivity whereas allergic asthma was singularly associated with excessive alpha-adrenergic responsiveness. Autoantibodies against beta-receptors were found predominantly in subjects with beta-adrenergic hyporeactivity. The presence of these autoantibodies and the physiologic abnormalities associated with their presence suggests a causitive relationship.