The impact of renal failure on the elimination and hydrolysis of three sources of tyrosine for parenteral nutrition, the dipeptides alanyltyrosine (Ala-Tyr), glycyltyrosine (Gly-Tyr), and N-acetyltyrosine (NAc-Tyr) was investigated in eight patients on regular hemodialysis therapy (HD) and seven healthy controls (CON). In CON, whole body clearance (Ctot) of Ala-Tyr (3,169 +/- 198 ml/min) was higher than Gly-Tyr (1,781 +/- 184, P less than 0.001), and both exceeded NAc-Tyr (284 +/- 24, P less than 0.001). In HD, Ctot of Ala-Tyr was not different from CON, but Ctot of Gly-Tyr (858 +/- 73, P less than 0.001) and NAc-Tyr (129 +/- 30, P less than 0.02) was decreased. The rise in plasma levels of constituent amino acids was higher in Ala-Tyr vs. Gly-Tyr (P less than 0.01). In HD, the pattern was similar, although the increase in Tyr was less than in CON. Plasma Tyr did not increase with NAc-Tyr in either group. Urinary loss of peptides was neglible, but 60% of NAc-Tyr infused was excreted by CON. The half-life of peptides incubated in CON and HD plasma was unchanged for Ala-Tyr (12.3 +/- 0.9 vs. 14.6 +/- 1.9 min) and prolonged for Gly-Tyr in HD (101.7 +/- 4.9 vs. 131.3 +/- 12, P less than 0.05). Thus renal failure does not impair Ala-Tyr disposal and delays Gly-Tyr utilization. These differential effects on peptide assimilation underscore the importance of peptide structure on metabolism. Both peptides, but not NAc-Tyr, may serve as a nutritional substrate in renal failure patients.