The authors determined whether response to cholecystokinin-tetrapeptide (CCK-4) was dose-dependent. Healthy volunteers (n = 36) received double-blind injections of either 9 micrograms, 25 micrograms, or 50 micrograms of CCK-4 and placebo in a randomized sequence of injection. Significant dose-related differences were found for the number of symptoms, sum intensity of symptoms and the time until onset of symptoms, but not for the duration of symptoms. The incidence of panic attacks with CCK-4 was 11%, 17% and 47% for the 9 micrograms, 25 micrograms and 50 micrograms dose, respectively. None of the controls panicked with placebo injections. These results support the notion of a dose-dependent effect of CCK-4-induced panic symptoms. Implications of these findings in the neurobiology of panic attacks are discussed.