The chemical syntheses of C-terminally shortened analogues of C3a, which is the best investigated anaphylatoxin and derives from the third component of complement system, is reported. The peptide assembly was performed with the solid-phase technique using a polyamide support and an orthogonal protection strategy. The base-labile Fmoc group was chosen for N alpha protection in combination with acid-labile side-chain protection. Excellent acylation yields could be obtained using HBTU (O-benzotriazolyl-N,N,N',N'-tetramethyluronium hexafluorophosphate) as activating reagent. With this methodology we synthesized eighteen different peptides with the following modifications: Varying the peptide length by sequential addition of glycine or arginine residues, prolongating the N-terminus with the Fmoc- or Fmoc-aminohexanoyl residues and exchanging the glycine in position 74 for alanine or D-alanine. We obtained two C3a analogues, Fmoc-YRAAALALAR and Fmoc-Ahx-YRRGRAAALGLAR, which were shown to be substantially more active than native C3a in the guinea-pig-platelet assay.