Research on the emergence of human avoidance behavior in the absence of direct contact with an aversive event is somewhat limited. Consistent with work on derived relational responding, the present study sought to investigate the transformation of avoidance response functions in accordance with the relational frames of Same and Opposite. Participants were first exposed to nonarbitrary and arbitrary relational training and testing in order to establish Same and Opposite relations among arbitrary stimuli. The training tasks were; Same-A1-B1, Same-A1-C1, Opposite-A1-B2, Opposite-A1-C2. Next, all possible combinatorially entailed (i.e., B-C and C-B) relations were tested. During the avoidance-conditioning phase, one stimulus (B1) from the relational network signaled a simple avoidance response that cancelled a scheduled presentation of an aversive image and sound. All but one of the participants who met the criteria for conditioned avoidance also demonstrated derived avoidance by emitting the avoidance response in the presence of C1 and the nonavoidance response in the presence of C2. Control participants who were not exposed to relational training and testing did not show derived avoidance. Implications of the findings for understanding clinically significant avoidance behavior are discussed.