We evaluated in patients suffering from COPD-related pulmonary hypertension whether nifedipine therapy lowers acutely and chronically pulmonary vascular pressure and resistance and whether pulmonary transmural pressure may be further lowered by the combined use of nifedipine and oxygen. Changes of the pulmonary vascular tone were determined on the pulmonary driving pressure/flow curve, which was generated by upright exercise. Fifteen patients with COPD and mean pulmonary pressure greater than or equal to 20 mm Hg were studied at control (Week 0) and after 1 wk of nifedipine treatment (180 mg daily, Week 1). It was possible to pursue the same nifedipine daily dosage for 2 months in 10 patients, who were re-evaluated after 8 wk of treatment and after nifedipine withdrawal the following week. At Week 1, mean pulmonary transmural pressure was reduced (32.8 +/- 4.1 versus 27.3 +/- 2.8 mm Hg, mean +/- SE, p less than 0.05) via active pulmonary vasodilation because the pulmonary driving pressure/flow curve was shifted right and downward. Both mean transmural pulmonary pressure lowering effect and active pulmonary vasodilatation regressed during long-term nifedipine treatment. Oxygen reduced pulmonary transmural pressure (32.8 +/- 4.1 versus 28.6 +/- 2.9 mm Hg, p less than 0.05, Week 0); however, this effect always disappeared during nifedipine treatment. We conclude that nifedipine should not be used as long-term treatment for COPD-related pulmonary hypertension and that nifedipine inhibits the oxygen capability to reduce pulmonary pressure.