The study objectives were to analyze the changes in exhaled carbon monoxide (COex) induced by histamine provocation challenge in asthmatic patients and to evaluate the relationship between COex and airway sensitivity and reactivity. Levels of COex were measured in 105 nonsmoking mildly asthmatic subjects before and after histamine provocation challenge. Dose-response curves were characterized by their sensitivity (PD20) and reactivity. Dose-response slope (DRS), continuous index of responsiveness (CIR), and bronchial reactivity index (BRI) were determined as reactivity indices. Bronchial challenge was positive for 47 subjects and negative for 58. The COex levels rose significantly after bronchial challenge in the positive response group (4.49 +/- 0.4 vs. 5.74 +/- 0.57 ppm, p = 0.025) and in the negative response group (2.84 +/- 0.25 vs. 4.00 +/- 0.41 ppm, p = 0.000). An inverse relation between basal COex and PD20 was found (r = -0.318, p = 0.030). In all subjects, a proportional direct relationship between COex and DRS (r = 0.214, p = 0.015), CIR (r = 0.401, p = 0.000), and BRI (r = 0.208, p = 0.012) was observed. On stepwise multiple linear regression analysis, COex only significantly correlated with CIR (multiple r2 = 0.174, p = 0.000). In conclusion, exhaled CO determination is a noninvasive inflammatory marker of the respiratory tract, which shows an acceptable association with airway hyperresponsiveness.