Glutamine-containing dipeptides may serve as a source of glutamine in parenteral nutrition solutions. To study the metabolism of glycyl-L-glutamine (gly-gln) and L-alanyl-L-glutamine (ala-gln) bolus injections of both dipeptides (0.1 mmol/kg within 40 seconds) were performed in five healthy male volunteers. Furthermore, plasma hydrolase activity against both peptides was tested by in vitro incubation. Both peptides were rapidly cleared from plasma after injection; however clearance was significantly greater for ala-gln than for gly-gln (1,595 +/- 124 v 507 +/- 14 mL/min). Arterial concentrations of constituent amino acids rose after peptide injection, indicating hydrolysis of the peptides. Glutamine concentration, for example, rose from 573 +/- 29 to a maximum of 718 +/- 34 mumol/L after gly-gln and from 570 +/- 15 to 900 +/- 53 mumol/L after ala-gln injection. Both peptides were hydrolyzed by plasma hydrolases during in vitro incubation. Hydrolysis was greater for ala-gln than for gly-gln. Half-lives of ala-gln and gly-gln were 46 +/- 3 and 553 +/- 160 minutes, respectively. For both peptides, plasma hydrolysis was too low to contribute significantly to in vivo clearance. Our results indicate that gly-gln and ala-gln are suitable sources for glutamine in parenteral nutrition solutions. Furthermore, plasma hydrolases do not play a significant role in peptide metabolism. Both peptides therefore appear to be primarily metabolized via extracellular hydrolysis, presumably by hydrolases on the cell membranes and consecutive uptake of the liberated amino acid residues.