In order to study the metabolic fate of prazepam (PZ), a new synthetic method of [5-14C]PZ(I) and [sidechain-14C]PZ (II) was investigated. The synthesis of these labelled compounds has already been described by E. J. Merrill, et al., but their method requires many synthetic steps and the yield is unfavorably poor. We have recently found much more convenient and efficient method, which is summarized below. 2-Iodo-4-chloroaniline was cyanized with Cu14CN obtained from K14CN, then reacted with phenylmagnesium bromide, hydrolyzed with conc. HCl to give [carbonyl-14C]2-amino-5-chloro-benzophenone(ACB). ACB was bromoacetylated, aminated with NH3 in MeOH, then heated and cyclized to [5-14C]desalkylprazepam(DPZ) according to the usual procedure. DPZ was converted to its Na salt with MeONa, then reacted with cyclopropylmethyl bromide in DMF to give I (2.61 mCi/mmol) with the overall yield of 41.9% from K14CN. [5-14C] Diazepam was also obtained by using MeI instead of cyclopropylmethyl bromide. On the other hand, 14CO2 generated from Na214CO3 and H2SO4 was reacted with cyclopropylmagnesium bromide to give [carboxyl-14C]cyclopropanecarboxylic acid, which was reduced with LiAlH4, then naphthalenesulfonylated to [alpha-14C]cyclopropylmethyl 2-naphthalenesulfonate. Na salt of DPZ was treated with the naphthalenesulfonate in DMF to give II (3.45mCi/mmol) with the overall yield of 36.9% from Na214CO3.