Dietary supplementation with fatty acids was carried out to examine whether the type and timing of dietary manipulation would have an effect on transfusion-induced immunosuppression in a rat cardiac transplant model. Linoleic acid (LA), oleic acid (OA), and fish oil (FO) were used because of their different effects on arachidonic acid (AA) metabolism. Pretransplant inhibition of AA metabolism (OA) shortened graft survival when compared with water-fed controls. Posttransplant LA (AA precursor) significantly prolonged graft survival. Pre- and posttransplant supplementation of LA and OA resulted in even more prolongation and shortening of graft survival, respectively. These findings suggest that transfusion-induced immunosuppression is partially mediated by AA metabolites, which are necessary for the pretransplant induction and posttransplant maintenance of the suppressed state. Dietary immunoregulation of transfusion induced immunosuppression is possible. The timing of dietary intervention and type of lipid supplementation is important in regulation of the immune response.