The present study used a basic behavioral paradigm derived from Relational Frame Theory (RFT), a contemporary behavioral account of language and cognition, to validate principle-based definitions of the cognitive interventions of defusion and reappraisal. Ninety-one participants first underwent an RFT learning paradigm that established symbolically generalized avoidance. Participants were then randomized to a defusion, reappraisal, or control condition. The main outcomes were equivalence responding—indicative of the trained relational network and analogous to the content of cognition—and avoidance—analogous to the behavioral impact of cognition. Defusion and reappraisal significantly reduced avoidance responding, providing support for the hypothesis that these interventions target the behavior of relational framing. Mediation analyses, conducted on an exploratory basis, revealed differences between the mechanisms of defusion and reappraisal and provided preliminary support for the classification of these interventions as a functional context intervention and a relational context intervention, respectively.