Oxygen radicals have been implicated in a variety of disease processes including asthma. In this study we investigated the production of superoxide by airspace cells in 56 patients with asthma as compared with 49 normal controls. We found that with patients with asthma with a forced expiratory vital capacity in the 1st second (FEV1) of less than 80% (n = 13) had higher spontaneous superoxide (SO) production when compared with normal subjects (3.6 +/- 1.0 versus 1.9 +/- 0.2 nmol/5 x 10(5) cells/hour, p < 0.01), whereas those with FEV1 > 80% (n = 40) were similar to normal subjects in superoxide generation (2.1 +/- 0.3 nmol/5 x 10(5) cells/hour). Airspace cells from patients with mild asthma and those with moderate asthma had higher phorbol myristate acetate (PMA)-stimulated SO production when compared with those from normal subjects (8.9 +/- 0.7, 11.1 +/- 2.4, and 6.5 +/- 0.4 nmol/5 x 10(5) cells/hour respectively, p < 0.005, r = -0.35, both comparisons). However, PMA-stimulated SO production was similar in both asthmatic subgroups. Finally, spontaneous generation of SO inversely correlated with FEV1% prediction (r = 0.35, p < 0.01) in the asthma group. We conclude that worsening of airway obstruction in asthma is associated with increased spontaneous generation of SO by airspace leukocytes.