Impaired insulin secretion has been observed during surgical stress in man. To determine the relationship between insulin secretion during anesthesia and surgical stress and plasma levels of norepinephrine (NE) and epinephrine (Epi), studies were performed in 16 patients before and during elective minor surgical procedures. In 8 patients studied during halothane inhalation anesthesia before operation, the acute insulin response (AIR) to glucose (5 g, IV) fell to 51 +/- 3% of the preanesthesia AIR (mean +/- SEM; P < 0.001). This inhibition of AIR appeared unrelated to increased adrenergic activity, since during anesthesia alone, plasma NE did not change significantly and plasma Epi fell from 94 +/- 11 to 34 +/- 10 pg/ml (P < 0.01). During the postoperative recovery period in these patients, after discontinuation of the anesthesia, the AIR to glucose was 50 +/- 5% of the preanesthesia baseline response (P < 0.001). At this time, both plasma NE and Epi were increased compared to preanesthesia levels [NE: 240 +/- 40 (preanesthesia) vs. 340 +/- 43 (postoperative); Epi: 219 +/- 43 (preanesthesia) vs. 94 +/- 11 (postoperative); both P < 0.05]. In eight patients undergoing similar operations during low spinal anesthesia, no inhibition of the AIR to glucose occurred, and plasma NE and Epi did not increase significantly during or after the operation. During the recovery period, there was a relationship between plasma Epi and the degree of inhibition of the AIR to glucose (r = 0.70; n = 11; P < 0.05). Thus, inhibition of insulin secretion during surgical stress may be mediated both by direct effect of the anesthesia used and by activation of the sympathetic nervous system.