AbstractTritium labelling of the enkephalinase inhibitor, thiorphan, is complicated by the presence of mercapto functional group. Reactions often used in aromatic tritiation, such as halogination and catalytic halogen/tritium displacement, are adversely affected by the presence of the divalent sulfur moeity. By protecting the SH group witht‐butyl group, the tritiation reaction proceeded smoothly without catalyst poisoning. The mercapto functionality was re‐generated with great ease and efficiency using 2‐nitrobenzenesulfenyl chloride and dithiothreitol (DTT). [3H]‐Thiorphan, thus, obtained had a radiochemical purity of >99% by AN‐HPLC and a specific activity of 18.42 Ci/mmol. [3H]‐Thiorphan showed good stability when stored at 4°C in an aqueous solution containing 10% methanol and 0.2% DTT in the dark. Copyright © 2008 John Wiley & Sons, Ltd.