OBJECTIVE: This study tested the hypothesis that compared to other DSM- IV specific phobia types, situational specific phobias have more in common with panic disorder and agoraphobia. METHOD: Responses to hyperventilation and CO2 inhalation were compared across groups of patients with the four main DSM-IV specific phobia types, a group with panic disorder, and a group of comparison subjects with no anxiety disorder (N = 15 per group). RESULTS: Although these challenges have been shown previously to distinguish patients with panic disorder from other groups, no groups differed significantly in their responses to hyperventilation. In addition, whereas the patients with panic disorder responded more to the CO2 challenge than did the normal subjects, the specific phobia groups did not differ from one another or from the other groups on most measures. For the few CO2 measures on which specific phobia groups differed, patients with situational and natural environment phobias showed the greatest response. CONCLUSIONS: Overall, these findings provided only limited support for the hypothesis that situational specific phobias are related to panic disorder.