Is caffeine withdrawal the mechanism of postoperative headache? This study examined the hypothesis that headache after general anesthesia is related to a caffeine withdrawal state. Two hundred eighty-seven patients undergoing minor elective procedures under general anesthesia were studied. Four to six hours after anesthesia each patient completed a questionnaire assessing his or her own alcohol, tobacco, and caffeine consumption, and the occurrence of postoperative side effects. A highly significant difference was found between the caffeine consumption of patients with and without preoperative (P = 0.0035) and postoperative (P less than 0.0001) headache. Logistic regression analysis of trend between headache and caffeine consumption suggested that with each 100-mg increase in caffeine consumption, there was a 12% increase in the odds of headache developing in the immediate preoperative period (P less than 0.0066) and a 16% increase in the odds of postoperative headache developing (P less than 0.0001). No relationship was found between headache and the patients' age, sex, usual frequency of headache, consumption of alcohol or nicotine, or the anesthetic agents or adjuvants used. It is concluded that postoperative headache is related to caffeine intake and that this relationship is explained, at least in part, by a perioperative caffeine withdrawal syndrome. 