A greater MAC fraction of nitrous oxide than isoflurane is required to prevent response to verbal commands and suppress the capacity to learn. Speculating that this difference between these agents may be caused by nitrous oxide's capacity to increase sympathetic activity, we tested the hypothesis that nitrous oxide may antagonize the suppression of learning found with isoflurane. We administered a combination of isoflurane and nitrous oxide at three subanesthetic test concentrations (0.43, 0.56, and 0.68 MAC) to 24 healthy male volunteers. Assuming additivity of the anesthetics, the first test concentration was selected to suppress learning of new information by 50% (ED50 for suppression of learning); the second concentration, to suppress the ability to respond appropriately to verbal command by 50% (MAC-awake); and the third, to provide 1.4 times MAC-awake. Three tests of learning were applied. At each test concentration, we provided 7 answers to "trivial pursuit"-type questions, resulting in a set of 21 answered questions for each volunteer; an additional 7 unanswered questions served as controls. At the highest test concentration, each volunteer also heard two examples from each of two categories (4 words) repeated 30 times (the category-example task), and a message instructing them to touch either their nose or their ear during a specified interval in the postanesthetic interview (the behavior task). The MAC-awake value for the combination of isoflurane and nitrous oxide was 118 +/- 4% of the expected value (i.e., the two anesthetics were antagonistic for this effect). Consistent with antagonism, the anesthetic concentration predicted to suppress learning by 50% permitted significantly more learning, and the ED50 was 105 +/- 2% of that predicted. Neither the category task nor the behavior task demonstrated evidence of learning at 1.4 times MAC-awake. Our results are consistent with an antagonism between nitrous oxide and isoflurane; however, the degree of antagonism is small.