Abstract: AIM: To study the influence of fluoextine on the metabolism of dextromethorphan (DM) in 19 healthy Chinese subjects. METHODS: All subjects took 20 mg DM before and 10 days after fluoxetine therapy. The volume of 0～8 h urine was measured and the concentration of DM and its metabolite dextrophan (DX) in the urine were determined. Thereafter, the metabolic ratio (MR) of DM and the recovery of DM and DX in 0～8 h urine were calculated. RESULTS: The mean MRs at baseline and after fluoxetine therapy in 19 subjects were 0.03±0.04 and 0.09±0.07, respectively(P<0.01). Of these subjects, while the MRs for 8 very extensive metabolizers (VEMs) were 0.005±0.004 and 0.026±0.012(P<0.01), the MRs for 11 intermediate metabolizers (IMs) were 0.05±0.04 and 0.13±0.06 before and after fluoxetine therapy, respectively(P<0.01). However, no subject showed MR in the range of poor metabolizer (PM) after fluoxetine therapy. The 0～8 h recoveries of DM before and after fluoxetine were 1.0%±0.9% and 1.2%±0.9%(P>0.05) and the values of DX were 40%±16% and 20%±14%(P<0.01), respectively. CONCLUSION: This study suggests that fluoxetine significantly inhibit the metabolism of dextromethorphan in Chinese subjects.