Abstract The protective actions of allopurinol in ischemic/reperfusion injury seem critically determined by the drug pretreatment regimen and may involve generalized alterations in tissue antioxidant status. In the present study, 12 male swine to be used as donors and recipients in a heart-lung transplantation study were treated with allopurinol given orally at a dose of 50 mg kg for 4 days prior to surgery. Red cells from allopurinol-treated animals showed a progressive decrease in susceptibility to in vitro peroxidative challenge. Although the degree and time-course of protection showed some degree of interanimal variation, maximal effects were obtained in most animals after 2–3 days. The extent of red cell protection in both donor and recipient animals correlated significantly with the functional viability of the transplanted lung, as assessed by tissue water content. It is suggested that the susceptibility of red cells to in vitro oxidative damage may provide a useful functional assessment of generalized alterations in antioxidant status produced by pharmacological interventions.