<p>Guayulins A and B, cinnamic and anisic acid esters respectively, are key components of guayule (<i>Parthenium argentatum</i> Gray) resin and guayulin A may be a contact allergen. In this report, we describe how transgenes expressed to increase rubber yield unexpectedly suppressed guayulin synthesis. Characterization of resin components (guayulins A and B) were carried out in three contrasting breeding lines of guayule plants, namely AZ-101, AZ-2, and N6-5 transformed with at least one of three different genes (farnesyl pyrophosphate synthase (FPPS), geranylgeranyl pyrophosphate synthase (GGPPS), and a mutated form of GGPPS, hexa-heptaprenyl pyrophosphate synthase (HHPPS)) through <i>Agrobacterium tumafaciens</i>-mediated transformation of leaf discs, followed by plant regeneration, acclimation and field trials. The transgenic guayule plants analyzed were shown to have either unaltered or enhanced resin levels. However, when the levels of guayulins were quantified, although concentrations varied throughout the year, both guayulin A and guayulin B were significantly lower in some transgenic plants than in wild type and empty vector control plants. Guayulin levels were especially low at the end of two years of growth, when the plants are normally harvested. Overall, overexpression of allylic pyrophosphate synthase genes, especially FPPS and HHPPS, suppressed the endogenous guayulin levels in transgenic plants and their seed-generated progeny plants. The deliberate development of guayule lines with low guayulin levels may help keep the concentrations well below potentially sensitizing levels in occupationally exposed workers, especially in situations where they need to handle crude resin extracts.</p>