Based on the hypothesis that blood platelets contribute to the pathogenesis of hypoxemic pulmonary hypertension in patients with chronic obstructive pulmonary disease (COPD), the effect of a prolonged treatment with dipyridamole, a platelet-inhibiting drug, on hypoxemic pulmonary hypertension was evaluated in a double-blind cross-over study. Eight patients with COPD, pulmonary hypertension [mean systolic pressure 52.2 ± (SD) 9.7 mm Hg; mean diastolic pressure 25.8 ± (SD) 6.8 mm Hg] and shortened platelet regeneration time [mean 5.2 ± (SD) 1.2 days] received, in a cross-over random sequence, the following two 3-month treatments: (a) dipyridamole 100 mg and acetylcysteine 100 mg every 6 h; (b) acetylcysteine, 100 mg every 6 h. Dipyridamole significantly prolonged the platelet regeneration time [mean 6.5 ± (SD) 1.0 days; p < 0.05]. There was no significant effect on diastolic pulmonary pressure. However, systolic pressure was significantly (p < 0.05) lower after dipyridamole [46.8 ± (SD) 16 mm Hg] than after placebo [56.1 ± (SD) 14 mm Hg]. These results suggest that dipyridamole can slow the progression of hypoxemic pulmonary hypertension in patients with