Technical Abstract: Recent research indicates that oral supplementation of NCG, an analogue of N-acetylglutamate, increases plasma arginine concentrations and growth rate in sow-reared piglets. To investigate the mechanism involved in this response, nursing piglets (n = 14; BW = 2.75 kg) were orally administered 50 mg/kg BW of NCG or saline twice daily from 7 to 14 d of age. After an overnight (12-h) fast, 14-d old piglets were administered saline or NCG at time 0 and 60 min, then received a flooding dose of [3H]phenylalanine in order to measure protein synthesis. At 90 min, the piglets were euthanized and tissue samples were collected. NCG-treated pigs gained more weight during the 7-d trial than control pigs (1.63 +/- 0.07 vs. 1.43 +/- 0.06 kg respectively; P < 0.001). Plasma arginine concentrations were 44% higher in NCG-treated pigs compared to control pigs (P < 0.01). NCG-treated pigs tended to have higher plasma insulin concentrations compared to control pigs (P < 0.06). Plasma glucose concentrations were not different between the treatments (P > 0.73). Fractional protein synthesis rate in longissimus dorsi muscle was 17% higher in NCG-treated pigs compared to controls (6.9 +/- 0.5 vs. 5.9 +/- 0.6 %/d respectively), although this did not reach significance (P < 0.24). Fractional rates of protein synthesis in liver, kidney, and duodenum were not different between treatments (P > 0.49). We postulate that the sensitivity of muscle protein synthesis to NCG treatment in piglets may be reduced in the fasted state. Oral NCG administration increases growth rate of nursing piglets likely by increasing plasma arginine concentrations.