The aim of this study was to evaluate the activity of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) on 52 patients affected with chronic obstructive pulmonary disease (COPD). The study was carried out in a randomized, parallel, double-blind trial, followed by incomplete blocks design. Pidotimod 800 mg was administered orally twice a day for 30 days. The follow-up period was 5 weeks. Our results show that in patients with COPD pidotimod potentiates T-cell activity. The effects on T-cells appear after 15 days of treatment and last for 5 weeks after the end of therapy. Since other studies demonstrated that pidotimod displays an immunopotentiating activity also on macrophages and granulocytes, the drug is useful to increase the immune defense during infections. The drug has a good compliance and is well tolerated also during long-term treatment.