The forensic application of stable isotope analysis to cocaine and heroin for geolocation of exhibits must take into account the possible enrichment and/or depletion of 13C and 15N during the illicit manufacturing process. Continuous-flow elemental analysis-isotope ratio mass spectrometry was utilized to measure changes in the stable isotope ratios of carbon and nitrogen for both cocaine (N = 92) and heroin/morphine (N = 81) exhibits derived from illicit manufacturing processes utilized by South American clandestine chemists. In controlled settings in South America, there was no siginficiant carbon isotope fractionation during the conversion of cocaine base to cocaine HCl using current illict methodologies. In contrast, nitrogen isotope fractionation for this conversion was 1‰. There was a kinetic carbon isotope ratio fractionation during the acetylation of Colombian morphine to heroin and as a result heroin exhibits will almost always have more negative δ13C values than the original morphine. There was an isotopic fractionation against 15N during the acetylation of morphine base to heroin base, but this effect was not expressed since all of the heroin base was precipitated during the manufacturing process. However, the clandestine process of converting a single batch of heroin base usually involved two consecutive crops of heroin HCl and the latter crop was isotopically depleted as expected from a Rayleigh distillation process. When heroin was deacetylated to morphine, the morphine produced resulted in δ13C values that were indistinguishable from the original morphine. The kinetic carbon isotope fractionation factor for the South American process of morphine acetylation was -1.8‰, allowing calculation of the δ13C values of the acetic anhydride from deacetylated heroin δ13C values.