The epoxidation of secondary high-molecular-weight guayule rubber to yield epoxidized guayule rubber (EGR) and the subsequent opening of the oxirane rings by fluoroacids to yield fluorinated guayule rubber (FGR) were reported in an earlier article.(1) The oxirane and hydroxyl groups that occur in EGR and FGR, respectively, enable these derivatives to be integrated into the binder system of coatings. The coating industry has long been interested in nontoxic multifunctional crosslinking agents that do not emit volatile organic compounds (VOCs). Ring-opening reactions of epoxides and reactions between hydroxyl and isocyanate groups are prime examples of crosslinking that do not emit VOCs. This study was conducted to ascertain the viability of guayule rubber derivatives that contain epoxide and hydroxyl groups as crosslinking agents in solvent-based coatings and powder coatings.