In order to evaluate the long-term effect of total parenteral nutrition supplemented with glutamine after surgery, patients (n = 17) undergoing elective abdominal surgery were randomized into two groups and studied for 30 days after surgery. During the 3 days immediately after surgery, one group (n = 8) was given total parenteral nutrition including a conventional amino acid solution (control group). The other group (n = 9) was given isocaloric and isonitrogenous total parenteral nutrition including the same amino acid solution supplemented with the dipeptide, glycyl-glutamine (GLN group). Oral food intake started on the third postoperative day and was gradually increased at will. The concentration of free amino acids in percutaneous muscle biopsy specimens was determined preoperatively and on days 3, 10, 20, and 30 after the operation. Free glutamine decreased in skeletal muscle in the control group on days 3 and 10 by 32.2 +/- 5.4% (p < .01) and 20.1 +/- 6.9% (p < .05), respectively. In the glycyl-glutamine group, the decrease in glutamine was delayed until day 10 when it was 22.1 +/- 8.1% (p < .05). The glutamine levels were restored on days 20 and 30 in both groups. Total parenteral nutrition supplemented with glutamine maintained the free glutamine levels in skeletal muscle after surgery, but when treatment was discontinued, the glutamine concentration in muscle dropped, despite a normal enteral dietary intake.