The hypothesis that bronchial hyperresponsiveness in asthma is influenced not only by environmental but also by intrinsic cellular factors was studied. We compared leukocyte responsiveness in asthmatic children with high (Group A) or low (Group B) bronchial responsiveness and in healthy children (Group C). Leukocyte responsiveness was assessed by the generation of superoxide anion (O-2) and the release of histamine after challenge with calcium ionophore A 12387 in the presence of calcium, and with deuterium oxide (D2O). Bronchial responsiveness was graded on the basis of response to inhaled histamine and exercise. The mean generation of O-2 and mean release of histamine by the calcium ionophore A 12387 and calcium were significantly greater in the asthmatics than in the healthy subjects (p less than 0.05). The mean release of histamine, but not the mean O-2 generation, was greater in Group A than in Group B (p less than 0.025). After D2O challenge a significant difference was found in the mean O-2 generation (p less than 0.05) and the mean histamine release (p less than 0.025) between asthmatic and healthy children. Between Groups A and B, the mean histamine release but not the O-2 generation was significantly different (p less than 0.025). The generation of O-2 and release of histamine were significantly correlated (r = 0.45, p less than 0.01). The results suggest that there is a basic intracellular abnormality that causes increased bronchial hyperresponsiveness.