The characteristic arteriopathy of primary pulmonary hypertension (PPH) with attendant endothelial dysfunction provides an opportunity for enhanced cellular activation in the lung. Data from many laboratories support the concept of altered eicosanoid metabolism in PPH. Rigorously quantitative measurements of the excretion of metabolites of thromboxane A2 and prostacyclin support persistent platelet activation and inadequate endothelial response in patients with PPH. Recent studies measuring excretion of prostaglandin D2 metabolites suggest that additional cell sources, such as activated tissue macrophages, may also play a role in the observed elevation in thromboxane excretion and possibly in the pathogenesis of the vascular remodeling. Additional research examining in vivo cell activation in patients receiving therapy with long-term infusion of prostacyclin may further our understanding of the pathogenesis of PPH.