The isotope ratio (15N and 13C) values for both illicit cocaine and heroin exhibits are altered by fractionation events during clean up and purification. Since illicit cocaine and heroin are not pure compounds but instead mixtures, to some degree the changes in exhibit isotope ratio reflect lesser amounts of other natural products as the materials are purified. Little attention has been given to the potential isotopic fractionations in going from raw plant materials to these finished alkaloid products. In the course of the authors' work with cocaine and heroin, they noticed isotopic differences in the free base and HCL ion-pair forms of these drugs; this requires explanation if isotope ratio analyses are to be used as a forensic tool in identifying the geographic origin of drugs. Ten clandestine chemists (six Colombian, three Peruvian, and one Bolivian) were allowed to process multiple kilograms of authentic Peruvian cocaine base into cocaine HCL in a controlled setting; and 12 Colombian chemists were allowed to process approximately 1 kilogram of authentic Colombian morphine into heroin HCL in a controlled setting. The materials and methods used are described in detail in this article. The results showed minimal carbon isotope fractionation in illicit cocaine processing, and values were not affected by different processing methods. Fractionation of 15N in illicit cocaine processing was detectable when not all of the cocaine was precipitated. The isotopic fractionation against 15N during the acetylation of morphine base to major crops of heroin base was minimal; however, considerable fractionation against 15N was detectable in the residual minor crops of heroin base. 6 tables and 19 references