This editorial permits personal conclusions and questions, hoping to stimulate relevant research. Klein, in 1959, serendipitously found that imipramine blocked the apparently spontaneous panic attack in non-depressed inpatients, later considered agoraphobic.Later it was found that these specific anti-panic drugs blocked lactate challenges, although low potency benzodiazepines and beta-blockers did not. Also, panic patients with early onset, frequently had a history of severe separation anxiety disorder, often manifested as school phobia. A series of usually post-pubertal panics led to severe chronic distress marked by fearful anticipation that the next panic would cause death or insanity. Avoiding situations (bridges, tunnels, freeways etc.) where help could not be readily obtained if panic reoccurred led to extensive travel restrictions and demands to be accompanied. These avoidances were misinterpreted as phobias, since there was no fear of cars or bridges per se. Family exhaustion led to psychoanalytic psychiatric hospitalization.1 In 1967, Pitts found, in placebo-controlled studies that intravenous sodium lactate in patients with spontaneous panics, then considered anxiety neurosis, could regularly cause such attacks. Further, other stressful infusions, such as EDTA, did not elicit panics, ruling out conditioning as a feasible alternative view. Later studies found inhaled 5%-7% carbon dioxide was similar to IV lactate as a panicogen, while willful room air hyperventilation was an uncommon panicogen. This contradicted the hyperventilation theory of panic disorder. Such panic reactions rarely occurred in patients with other anxiety disorders, other psychopathological states or normal subjects, except strangely, in women with severe chronic premenstrual syndrome.Groundbreaking therapies derived from this program. Panic disorder and agoraphobia were now quite treatable outpatient conditions, although unfortunately DSM-III distorted agoraphobia?s definition by simply choosing six frequent avoidances as criteria, while ignoring their common role in preventing flight to help, as well as the utility of a companion for travel.