OBJECTIVE Reduction of serum sex steroid levels has been reported to occur after the administration of beta-adrenergic medication. In that beta-adrenergic blockade is a central pathophysiologic feature of asthma, this study was done to explore the possibility of hormonal alteration in asthma. METHODS Sex steroids obtained from 22 postmenopausal asthmatic and 22 age-matched, postmenopausal, nonasthmatic women were assayed. No subject had received estrogens, progestins, or oral corticosteroids for 120 days before the study. RESULTS Mean dehydroepiandrosterone sulfate (DHEAS; p < 0.002), dehydroepiandrosterone (DHEA; p < 0.03), estradiol (p < 0.02), and estrone (p < 0.02) levels were lower in asthmatic patients compared with nonasthmatic subjects. Results could not be accounted for by current medication. Patients with asthma demonstrated no decrease in 17-hydroxyprogesterone or cortisol compared with nonasthmatic subjects, limiting findings to the delta 5, and not the delta 4, steroidogenic pathway. In a second phase of the study, DHEAS was measured before and after 3 days of oral beta-agonist stimulation in eight postmenopausal asthmatic women. Serum DHEAS concentration increased in eight of eight subjects, from a mean of 28.6 +/- 19.9 micrograms/dl (mean +/- SD) to 40.7 +/- 24.8 micrograms/dl (p = 0.002). Serum cortisol concentration was unchanged. CONCLUSIONS The results indicate that postmenopausal asthmatic women have lower serum levels of adrenally derived sex steroids than their nonasthmatic peers and that this anomaly may be ameliorated by adrenergic stimulation.