Abstract Trauma victims often suffer immune system failure. Oral arginine has strong immune-enhancing properties. The metabolic, hormonal, and immune effects of increasing concentrations of arginine as part of post-trauma intravenous hyperalimentation (IVH) were studied. Groups of 11–14 rats, 275–350 g, underwent jugular vein catheterization and bilateral closed femoral fractures under anesthesia. IVH was started immediately postinjury at a rate of 0.8-1 ml/100 g body wt/hr and continued for 5 days. Twenty percent dextrose and three different amino acid mixtures were given as follows: (A) FreII (1.55 g ARG/1); (B) FreIII (4.05 g ARG/1); (C) modified FreIII (7.9 g ARG/1). All rats lost weight over the 5-day postinjury period; however, rats in groups B and C lost significantly less weight than rats in group A (−3.4 ± 0.8% of initial body weight and −3.6 ± 0.9% vs −6.1 ± 1.2%, P < 0.05). Rats in group A had negative cumulative nitrogen balance, while those in groups B and C were in highly positive balance. No significant difference in body weight change or nitrogen balance was noted between groups B and C. Trauma-induced thymic involution as assessed by thymic weight and lymphocyte content was greatest in group A, which received the lowest amount of arginine, and was linearly abrogated by increasing the amount of arginine administered (A < B < C). Thymocyte immune responsiveness increased with the amount of arginine given as assessed by mitogenesis in response to Con A (stimulation index: A—151.3 ± 28.8 vs B—243.6 ± 29.2, P < 0.01 vs C—321.8 ± 22.3, P < 0.001 vs A and P < 0.02 vs B) and PHA (A—65.0 ± 14.3 vs B—67.7 ± 15.3, NS, vs C—117 ± 14.0, P < 0.005 vs A and B). It was concluded that (1) increased arginine administration in IVH decreases body weight and nitrogen loss postinjury; maximal anticatabolic effects occur at intermediate arginine levels; (2) high arginine levels increase thymus weight, thymic lymphocyte content, and in vitro blastogenesis of thymocytes to Con A and PHA; the immune effects show linear correlation to the amount of arginine administered; (3) the immune-enhancing properties of arginine are independent of its metabolic effects and this suggests that optimal arginine supplementation post trauma should be determined in terms of maximal immune responses.