There is increasing evidence for the role of basophils in the allergen-induced late asthmatic response (LAR). To study the effect of inhaled allergen on basophil function in subjects with asthma, ex vivo basophil spontaneous histamine release (SHR) in peripheral blood and plasma histamine was measured before and 2, 5, 10, and 15 minutes, and 2, 4, 6, and 8 hours after allergen bronchial challenge (allergen study day) in six subjects with atopic asthma. Allergen inhalation induced an early response and LAR consisting of a mean (+/- SD) 32.5% (+/- 7.9%) and 28.8% (+/- 7.7%) fall in FEV1, respectively. As a control for the effects of bronchoconstriction, on another occasion, methacholine challenge was performed to produce a mean 33.4% (+/- 3.4%) fall in FEV1 during the early response and no LAR, and blood was obtained to measure basophil histamine release (HR) and plasma histamine. There was a small, but significant (p less than 0.05), rise in median SHR from 4.6% to 6.1% of total basophil histamine after allergen but not after methacholine inhalation. HR remained high after allergen inhalation during the 8 hours of study, whereas it demonstrated a steady, significant, decrease between 4 to 8 hours after methacholine inhalation. No significant changes in plasma histamine were recorded on either allergen or methacholine study days. On a third occasion, SHR was measured after challenge with physiologic saline to control for any effects of methacholine on SHR, and a decrease in HR was recorded during the day similar to HR observed after methacholine challenge. These studies suggest an enhancing effect of inhaled allergen on SHR.(ABSTRACT TRUNCATED AT 250 WORDS)