The potential of various microbes to metabolize the dextromethorphan (DXM) , a CYP 2D6 substrate was studied to investigate similarities between microbial and mammalian metabolism. Eight microbes were screened for their ability to metabolize DXM in a manner comparable to humans with a view to develop alternative systems to study human drug metabolism. The major metabolite of DXM produced by Saccharomyces cerevisiae (NCIM 3090) was characterized by HPLC and Liquid Chromatography Mass Spectrometry (LC/MS). DXM was biotransformed by Saccharomyces cerevisiae into a major metabolite dextrorphan which is a known , active metabolite of DXM in human. The microbial metabolism of DXM was similar to the metabolism in mammals. The Saccharomyces cerevisiae could be used as a suitable model strain in vitro to mimic CYP 2D6 metabolism and to produce dextrorphan an active metabolite of DXM for further pharmacological, toxicological studies.