This study was designed to assess the effect of differential leukocyte depletion during chemotherapy by monitoring the levels of exhaled hydrogen peroxide H ₂O ₂ and nitric oxide (FeNO) present. In 39 patients with lung cancer (chronic obstructive pulmonary disorder up to stage II, median forced expiratory volume in one second 78% predicted), measurements were performed before a cycle of therapy (day 1), at least once during the cycle (day 8: n=34; day 15: n=19), and afterwards (days 21-29). There were significant changes in the level of H ₂O ₂, FeNo and peripheral blood cell differentials over the visits. The level of H ₂O ₂ was decreased only on day 15, with a median (difference between the upper and lower quartiles) fall of 31 (57)%, while FeNO was reduced only on day 8, by 22 (40)%. Neutrophil numbers were unchanged on day 8 and decreased by 59 (48)% on day 15, while monocyte numbers were decreased on day 8 by 87 (39)%. On days 21-29, values had returned to baseline. Taken together with previous findings, the parallel course of levels of exhaled hydrogen peroxide and neutrophil counts suggests that a major part of exhaled hydrogen peroxide is due to neutrophils via the conducting airways. In contrast, the production of exhaled nitric oxide seems to be primarily associated with monocytes.