SummaryF-18 labeled SR46349B, a highly potent and selective 5-HT2 receptor antagonist, was synthesized as a potential radioligand for PET studies of brain 5-HT2 receptors. Nucleophilic aromatic substitution of trans-1 -(2-nitrophenyl)-3-(4-methoxymethoxyphenyl)-2-propenone (UL) with NCA [18F]fluoride in the presence of potassium carbonate and kryptofix-222, followed by HC1 hydrolysis, gave F-18 labeled 12, which was purified by a novel combination of C-18 Sep-Pak and silica column chromatography. Subsequent condensation of [18F]ketone 12 with MezNCH2CH20NH2 gave a mixture of [18F]SR46349B and its geometric isomer, which was separated by high performance liquid chromatography. The three step hot synthesis of [*8F]SR46349B required 170 min. and gave a specific activity of 1140 Wmmol, 5% radiochemical yield (EOB) and 96% radiochemical purity.