Cognitive-behavioral treatments for panic disorder (PD) emphasize interoceptive exposure (IE) to target anxiety sensitivity (AS) but vary considerably in its manner of delivery. This randomized controlled trial was conducted to compare the efficacy of the low-dose delivery of IE exercises often prescribed in treatment protocols to an intensive form of IE hypothesized to optimize inhibitory learning. Participants (N = 120) with elevated AS were randomly assigned to one of four single-session interventions: (a) low-dose IE as prescribed in Barlow and Craske's Panic Control Treatment, (b) low-dose IE without controlled breathing or a lengthy between-trial rest period, (c) intensive IE, or (d) expressive writing control. Compared to the other conditions, intensive IE produced significantly greater reductions in AS and fearful responding to a straw breathing task from pretreatment to posttreatment. Maintenance of gains during the follow-up period did not differ between conditions. Changes in fear toleration and negative outcome expectancies fully mediated the superior efficacy of intensive IE over low-dose IE. The two low intensity IE conditions produced particularly high rates of fear sensitization on between-trial and outcome variables. The findings suggest that the intensive delivery of IE exercises has the potential to improve the efficacy of exposure-based treatments for PD.