(1) Intravenous glucose tolerance tests have been carried out on 6 migraine sufferers on two occasions. The first study was carried out during a migraine attack and the second was performed in an attack-free period. The patients had fasted overnight and the investigations were carried out in the morning. Samples of venous blood were taken for measurement of concentrations of glucose, lactate, pyruvate, free fatty acids (FFA), glycerol, ketone-bodies, insulin and growth hormone. (2) an impaired tolerance to glucose was found during the migraine attacks compared with the control studies. Elevated ketone and FFA levels were found during the attacks and may have accounted for the glucose intolerance. The elevation of plasma FFA levels during the migraine attacks paralleled changes in blood glycerol concentrations suggesting increased lipolysis during the attacks. Growth hormone and cortisol were raised and insulin was depressed during attacks. (3) Our observations, in which the patients acted as their own controls, imply increased lipolysis during migraine attacks and are in contrast to previously reported studies. The patterns of metabolic and hormonal changes are consistent with a stress response during the attacks and the significance in relation to the causation of the attacks is discussed.