The aim of this study was to investigate whether pretreatment with drugs that interfere with platelet functions in different ways could modify the pulmonary vascular response in a porcine septic shock model. Septic shock was induced by i.v. infusion of live Escherichia coli bacteria. Bacteriemic animals were divided into five groups: untreated or pretreated with a thromboxane-A2 synthetase inhibitor (UK 38 485), a serotonin-receptor antagonist (ketanserin), a combination of these two drugs, or a platelet antiaggregating drug (dipyridamole). E. coli induced significant pulmonary hemodynamic and respiratory changes. The pulmonary responses to E. coli infusion were attenuated after pretreatment with UK 38 485 but unaffected by prior administration of ketanserin or dipyridamole. The combined pretreatment did not attenuate the pulmonary hypertension or other pulmonary responses to E. coli more than UK 38 485 alone. Dipyridamole did not alter the pulmonary circulation after bacterial infusion. It was concluded that thromboxane-A2 is an important, but not the only, mediator of the pulmonary vascular response in septic-shocked pigs and that factors such as serotonin and platelet aggregability seem to be of minor, if any, importance for the hemodynamic response.