Here we report on a rare and opportunistic acoustic turn-taking with an adult female humpback whale, known as Twain, in Southeast Alaska. Post hoc acoustic and statistical analyses of a 20-min acoustic exchange between the broadcast of a recorded contact call, known as a whup/throp, with call responses by Twain revealed an intentional human-whale acoustic (and behavioral) interaction. Our results show that Twain participated both physically and acoustically in three phases of interaction (Phase 1: Engagement, Phase 2: Agitation, Phase 3: Disengagement), independently determined by blind observers reporting on surface behavior and respiratory activity of the interacting whale. A close examination of both changes to the latency between Twains calls and the temporal matching to the latency of the exemplar across phases indicated that Twain was actively engaged in the exchange during Phase 1 (Engagement), less so during Phase 2 (Agitation), and disengaged during Phase 3 (Disengagement). These results, while preliminary, point to several key considerations for effective playback design, namely the importance of salient, dynamic and adaptive playbacks, that should be utilized in experimentation with whales and other interactive nonhuman species.