Children with chronic asthma frequently receive "bursts" (less than 7 days) of short-term, high-dose prednisone (1 to 2 mg/kg/day) for acute exacerbations of their disease. Certain of these patients may also require inhaled corticosteroids (IC) for control. The effect of these "bursts" on the hypothalamic-pituitary-adrenal axis (HPAA) is unclear. To test the integrity of the HPAA in such patients, we measured plasma cortisol (F) in response to serial administration of insulin-induced hypoglycemia (nadir = 34 +/- 1.2 mg/dl; mean +/- SE), followed by 250 micrograms/1.73 m2 of synthetic ACTH in the following children with asthma: group I, seven patients who received no more than one "burst" per year (0.71 +/- 0.2); group II, six individuals who received more than one "burst" per year (3.6 +/- 0.2) and no IC; and group III, 10 subjects who received more than one "burst" per year (4.7 +/- 0.3) plus IC. All patients received daily theophylline and beta-agonists; seven patients were taking sodium cromolyn. No patients received troleandomycin. Compared to group I (control subjects), 16% of group II had a subnormal response of F to hypoglycemia. In addition, a subnormal response of F to hypoglycemia or ACTH was documented in 20% and 10% of group III, respectively. All individuals with a subnormal response of F to either hypoglycemia or ACTH received four or more "bursts" per year. We conclude that as a group, children affected by asthma treated with "bursts" alone or "bursts" plus IC appear to have a normal HPAA.(ABSTRACT TRUNCATED AT 250 WORDS)