The effects of repeated exercise-induced bronchospasm on nonspecific (nonallergenic) bronchial responsiveness (NSBR) to histamine were studied in 12 asthmatic patients (6 F, 6 M). Baseline NSBR, determined by the provocative concentration of histamine giving a 20% fall in FEV1 (PC20), ranged from 0.41 to 10.2 mg/ml (geometric mean +/- SD: 2.6 +/- 2.5). Each subject performed three consecutive exercises on the ergometer for 6 min at 70% of their VO2 max. Each test was preceded and followed by a histamine inhalation test (HIT). On a control day, 4 HIT were done at 1 h interval, without intercurrent exercise. A significant reduction in histamine responsiveness was observed on control day from the first to the fourth HIT. On exercise day, a mean percent fall in FEV1 of 19.4 +/- 12.9, 16.2 +/- 12.2 and 15.8 +/- 12.7 was observed after the three consecutive exercises but no significant difference could be found between the four PC20 measurements. Four subjects showed refractoriness to the second exercise and no change in the bronchial response to histamine was observed during the refractory period. In conclusion, (1) repeated exercises do not change NSBR; (2) the refractory period after exercise is not due to a change in NSBR, and (3) a tachyphylaxis to histamine occurs in some subjects after repeated inhalations of histamine.