High-density lipoproteins (HDL) were examined as potential carriers of small peptides in plasma. HDL purified by density gradient centrifugation was delipidated and fractionated by size-exclusion chromatography under denaturing conditions. By HPLC and mass spectrometry, more than 100 peptide components were found in the size range from 1000 to 5000Da. By sequence analysis, peptides were identified as fragments of proteins such as apolipoproteins, fibrinogen, α₁-proteinase inhibitor, and transthyretin. The results indicate that purified HDL bears a complex range of small peptides. It is unclear whether the peptides have any significant functional role as apolipopeptides, but they may represent a pathway for peptide delivery or scavenging and a significant reservoir of plasma peptides for diagnostic evaluation.