Of 57 patients with panic disorder with agoraphobia, more had their first panic in late spring and summer than in fall and winter, and in warm weather than in cold weather. In the month before the first panic 52% of the patients had prodromal depression or anxiety. Agoraphobic avoidance preceded the first panic in 23%, began within days after the first panic in 32% (without prodromal anxiety or depression in only 20%), and after more than one panic (1 week to 11 years later) in 41%. The site of the first panic was from the agoraphobic cluster (public places) in 81%, at work or school in 11%, and inside the home in 8%. Thirty-eight percent of patients were with a familiar adult at the time. Many features of the syndrome can be explained by an integrated model with several interacting factors contributing in varying degrees to the different routes by which it develops. To the learning and biological factors already suggested we add an evolutionary factor to explain why most first panics occur outside the home and mainly in public places. Certain extraterritorial cues constituting an agoraphobic cluster seem to be prepotent and prepared triggers or modifiers of fear during stress.