Several studies outline the imbalance of phagocyte functions in chronic obstructive pulmonary disease (COPD). In this regard, here, we have assessed either monocyte- and polymorphonuclear cell (PMN)-mediated chemotactic, phagocytic and killing capacities or PMN-triggered metabolic pathway in a group of COPD patients before and at different times after thymostimulin administration. Before therapy, an increase of O2-generation and a decrease of myeloperoxidase release were found in these individuals when compared to controls. Moreover, a reduction of either PMN-mediated chemotaxis and killing or monocyte chemotactic capacities was observed. By contrast, no differences were seen in terms of beta-glucuronidase release, monocyte-mediated killing and PMN or monocyte phagocytic function. During a one-year monitoring following immunotherapy, O2- production and myeloperoxidase activity fell within normal values, while phagocyte functional capacities were unaffected by such a treatment. Furthermore, COPD subjects exhibited a significant improvement of their clinical status as assessed during a one-year followup. All together, these findings suggest a potential role for thymostimulin in the treatment of COPD patients.