OBJECTIVE The authors examined the effect of panic provocation on the subsequent development of panic attacks and panic disorder in nonclinical subjects with no history of spontaneous panic. METHODS Sixty-two subjects who had completed a study examining fearful responses to a single vital capacity inhalation of 35% CO2 were reevaluated 1 year following the challenge test. RESULTS Challenge-induced panic was not related to the later development of panic or panic disorder. According to the Structured Clinical Interview for DSM-III-R--Non-Patient Edition, none of the subjects met DSM-III-R criteria for panic disorder and only six subjects reported spontaneous panic during the year after panic provocation. Of the six subjects who experienced spontaneous panic, two had panicked in response to the CO2 challenge. CONCLUSIONS The experimental provocation of panic in nonclinical subjects appears to be a safe research paradigm for exploring the psychopathogenicity of panic disorder.