BACKGROUND Post-lung transplant reperfusion edema (PLTRE) and its more severe form, primary graft failure (PGF), occur in 10% to 60% of lung transplant recipients. We hypothesized that PLTRE and PGF would be associated with an elevated proinflammatory cascade and that the allograft would be the source of cytokine appearance in the circulation. METHODS Pulmonary arterial and systemic arterial samples were obtained at baseline and at 4, 8, and 24 hours after reperfusion. Post-lung transplant reperfusion-edema and PGF were defined as PaO2/FiO2 less than 300 with a mild or moderate infiltrate, or less than 200 with a severe infiltrate and ventilator dependence after 72 hours, respectively. Tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-8, and IL-10 concentrations were determined by immunoassay. RESULTS Fifteen single and 6 bilateral lung recipients were studied. Six (29%) had PLTRE and 4 (19%) had PGF; these patients had an overall elevation in plasma IL-6, IL-8, and IL-10 concentrations (all p < 0.05). Subgroup analysis revealed a significantly greater elevation in IL-6, IL-8, and IL-10 levels in PGF patients (all p < 0.01) versus PLTRE. In the PGF group, TNFalpha and IL-10 concentrations were significantly greater in the systemic versus the pulmonary arterial samples (p < 0.05). CONCLUSIONS Patients with PLTRE and PGF exhibited graded increases in IL-6, IL-8, and IL-10 concentrations. The PGF patients had higher TNFalpha and IL-10 systemic arterial concentrations overall, consistent with the allograft being a source of this cytokine production.