The talk will describe synthesis of perfluoro-arene-modified phage-displayed libraries SXCXnC-phage, n=3–5, where X is any amino acid except for cysteine and their application to selection of albumin-binding macrocyclic peptides. Modification of traditional disulfide peptide libraries displayed on phage by decafluoro-diphenylsulfone (DFS), yields a genetically-encoded library of octafluoro-diphenylsulfone-crosslinked macrocycles (OFS-SXCXnC-phage). Selection from these libraries using albumin as bait and further testing of the selected peptides by 19F NMR and fluorescent polarization identified OFS-SICRFFC as the lead sequence. We replaced DFS with isosteric pentafluorophenyl sulfide (PFS) to remove undesired reactivity of DFS-macrocycles with biological thiols. The PFS-SICRFFCGG (14c) exhibited Kd = 4–6 µM towards human rat and mouse serum albumin. When injected in mice, the concentration of 14c in plasma for 3 hours was indistinguishable from SA-21 reference peptide. We tested in vivo circulation of analogs of 14c such as ala-mutants, linker-analogs, and N- and C-terminal payloads. We observed a similar in vivo retention for 14c and its analogs with polyethylene glycol (PEG) linker on C-terminus or a payload attached to such linker. Specifically, a conjugate of 14c and therapeutically relevant peptide apelin remained in circulation for 3 hours at concentrations similar unmodified 14c or SA-21 benchmarks; in contrast, unmodified apelin was cleared from the circulation after 2 minutes. The PFS-SICRFFC is the smallest known peptide macrocycle with a significant affinity for human, mouse and rat albumin and substantial in vivo circulation life. It is a productive starting point for future development of compact macrocyclic libraries with extended half-life in vivo.