Forty-three patients with panic disorder or agoraphobia with panic attacks and 20 control subjects received 0.5 M racemic sodium lactate intravenous infusions, single-blind as to duration and sequence. During the procedure, pulse; blood pressure; blood L-lactate and pyruvate; plasma ionized calcium, phosphate, prolactin, epinephrine, norepinephrine, and cortisol levels; and venous PCO2, pH, and bicarbonate were measured in an attempt to clarify the mechanism of lactate-induced panic attacks. During the infusion, 72% of the patients but none of the control subjects had panic attacks. The laboratory findings suggest that peripheral catecholamine surge is not the mechanism by which lactate causes panic, although elevated epinephrine may be a predisposing factor. Heightened central noradrenergic activity was present in many but not all of the attacks. Contrary to previous hypotheses, neither depression of ionized calcium nor induction of metabolic alkalosis appears sufficient to cause panic during lactate infusion.