BACKGROUND: Five percent to 10% of all fracture patients experience an inadequate healing process that results in a nonunion of fracture parts. Previous experimental studies have indicated the importance of sufficient nitric oxide production from arginine during normal fracture healing. However, during conditions of stress, such as inflammation, arginine availability can become limited, which may lead to a nonunion as a result of insufficient callus formation. OBJECTIVE: The aim of this study was to measure callus and plasma amino acid concentrations in patients with and without a fracture nonunion. DESIGN: Amino acid concentrations in plasma and callus were measured with HPLC in atrophic nonunions (n = 12) and compared with those in hypertrophic nonunions (n = 12), acute fractures (n = 15), and healed fractures (n = 8). RESULTS: Arginine (61 compared with 180 mumol/mg; P < 0.0001), citrulline (13 compared with 44 mumol/mg; P < 0.0001), and ornithine (25 compared with 149 mumol/mg; P < 0.0001) in callus were significantly lower in atrophic-nonunion patients than in healed-fracture patients. In hypertrophic nonunions, arginine was significantly higher and ornithine was lower than in healed fractures. Plasma arginine concentrations were significantly lower in patients with hypertrophic nonunions (62 mumol/L; P < 0.001) and acute-fracture patients (41 mumol/L; P < 0.001) but not in atrophic-nonunion patients. Plasma ornithine concentrations were lower in all groups than in acute-fracture patients. CONCLUSIONS: Amino acid concentrations were significantly changed in nonunion patients. Atrophic nonunions had lower concentrations of all amino acids, whereas hypertrophic nonunions had higher arginine and lower ornithine concentrations at fracture sites than did healed-fracture and acute-fracture patients.