This paper dedicated to Dr. Shahriyar Omidvar for his effective contribution in Iranian pharmaceutical industryA highly efficient and practical synthesis of C-terminal amidated peptides has been developed. According to this approach, amidation of the C-terminus of peptides was carried out using NH 4 Cl, alkylammonium chloride (RNH 3 Cl) and semicarbazide hydrochloride in the presence of TBTU as a coupling reagent and a tertiary amine as the base at room temperature in good to high yields. Some opioid peptides such as enkephalin derivatives were synthesized according to this novel method.