Introduction: Arginine deficiency occurs in trauma, and in cancer patients secondary to the up-regulation of the enzyme arginase I. Arginine is necessary for normal T lymphocyte function and for nitric oxide (NO) production. Its deficiency is associated with immune suppression. Arginase I expression is induced by Prostaglandin E2, a product from the metabolism of omega-6 fatty acids and by IL-13, a T helper 2 cytokine. The purpose of this study was to determine how different prostaglandins E1, E2, and E3 which are derived from borage oil, corn oil and fish oil respectively would affect the induction of arginase I and ultimately the utilization and availability of arginine. Methods: Macrophages (RAW264.7) were cultured with PGE1, PGE2, or PGE3 (0–10 μM). IL-13 (10 ng/ml) was added 24 hours later to induce arginase I. After twenty-four hours, cells were harvested and arginase activity was assayed by a Kornarska colorimetric method. In separate experiments, nitric oxide production was induced by adding endotoxin (LPS) and was measured using the Greiss reaction. Arginase I expression was evaluated by Western Blots (WB). Results: Arginase I activity (nmol/min/mg) and expression was induced by all prostaglandins but more by PGE1 and PGE2 than by PGE3 560.37(± 37.36), 473.06(± 59.64), and 242.65(± 21.05) respectively with control cells at 27.6(± 7.05) (p < 0.05). Western Blots showed a corresponding variance in arginase I expression. Prostaglandins synergized with IL-13 to induce arginase I but again PGE3 was associated with the least increase in arginase I expression. Mean nitrate levels (μM) were inversely proportional at 0.9(± 0 .11), 1.13(± 0.25), and 1.77(± 0.23) respectively (p < 0.05). Conclusions: PGE1 and PGE2 increase macrophage arginase activity and arginase I expression compared to PGE3. The type of predominating PGE from the metabolism of differing dietary PUFAs may have a direct impact on the metabolism of arginine, and arginine availability for T-cell function. This is an important consideration in determining the physiological consequence of different immune-enhancing dietary regimens.