Abstract: Atriopeptin Ⅲ(AP Ⅲ)and its small molecular analog were synthesizedmanually by stepwise solid-phase method. The peptides were oxidized with iodine in 30%acetic acid at very high dilution to form intramolecular disulfide bridge and purified tohomogeneity by conventional means, including Sephadex G15,dialysis and reversed-phaseHPLC. Bioassay study demonstrated that the synthetic AP Ⅲpossesses potent bioactivitiesidenticaI to those of the same product of Peninsula Lab both in vitro and in vivo;whereas thelinear peptide,having the same primary structure as AP Ⅲ,showed very limitedbioactivity. The small analog, with Ser-Ser-residue deleted from the N-terminal of AP Ⅲ.was equipotent as AP Ⅲ while exhibiting a longer half-life in vivo resulting from the peptidemodification.