Human C3a anaphylatoxin, the 77-residue polypeptide split from the NH2-terminus of the alpha chain of C3, causes contraction of smooth muscle, release of histamine from mast cells, and increase in vascular permeability. The 76-residue peptide formed by removing the COOH-terminal arginine from C3a shows none of these activities. In this study, oligopeptides from the COOH-terminus of C3a were synthesized by the solid-phase method and found to exhibit these inflammatory activities and to display the specificity of C3a. At a molar dose 50 times that required for C3a, the octapeptide with the sequence Ala-Ser-His-Leu-Gly-Leu-Ala-Arg stimulated histamine-mediated contraction of guinea pig ileum strips, released vasoactive amines from rat mast cells, and increased the vascular permeability of human and guinea pig skin. Since it cross-desensitized the ileum to C3a but not to C5a or bradykinin, the octapeptide specifically mimicked the action of C3a. It was not chemotactic for human neutrophils over a broad range of concentrations.