To indirectly test the hypothesis whether serotonin (5-HT) might have a role in the increase in pulmonary vascular resistance, we evaluated the haemodynamic and gas exchange response of intravenous ketanserin (K), a 5-HT receptor inhibitor, in eight severe but stable patients with chronic obstructive pulmonary disease with secondary pulmonary hypertension (mean pulmonary artery pressure (Ppa) 30.3 +/- 7.3 mmHg). Measurements were done at baseline, after oxygen breathing (2 L.min-1), K bolus (6-15 mg) and finally during oxygen breathing (2 L.min-1) added to K infusion (3-6 mg.h-1). K bolus induced a significant reduction of mean Ppa (p < 0.05), mean systemic arterial pressure (p < 0.01) and total systemic resistance (p < 0.01). Cardiac index (+7%), oxygen delivery (+7%) and pulmonary vascular resistance (magnitude of the reduction: -12%) did not change significantly. When oxygen was added to K infusion, the cardiac index significantly dropped when compared to K bolus (p < 0.05), but oxygen delivery remained stable because of the resulting increase in arterial oxygen concentration; against baseline, the mean Ppa showed the same magnitude of reduction as with oxygen breathing or K bolus alone (p < 0.05). Ventilation and gas exchange were not significantly influenced by K bolus. When we individually analysed the changes of pulmonary vascular resistances by plotting the driving pressure through the pulmonary circulation against the cardiac output, we observed that an active vasodilating effect on the pulmonary circulation occurred with K in only one patient, while in three other patients there was rather a recruitment effect of the pulmonary vessels due to the systemic effects of the drug. In conclusion, this study of a small number of patients with severe chronic obstructive pulmonary disease associated with pulmonary hypertension shows that the parenterally given serotonin antagonist ketanserin predominantly affects the systemic circulation. Our results do not support the hypothesis that in stable chronic obstructive pulmonary disease patients with pulmonary hypertension, serotonin might have a role in the increase of pulmonary vascular tone.