In a randomized controlled clinical trial, 14 patients requiring resection of tumors were divided in two groups: one group was anesthetized with nitrous oxide [67% N2O-33% O2 (vol/vol)] and the other with propofol. Two other groups of subjects were studied: a group of patients that was undergoing orthopedic procedures and was anesthetized with nitrous oxide [67% N2O-33% O2 (vol/vol)] and a control group (fasted for 10 hrs and no anesthesia). In patients requiring resection of tumors, the blood L-methionine concentration was significantly lower and the blood amino acid pattern was significantly affected after the administration of nitrous oxide (120-310 mins) compared with values after the induction of anesthesia and before surgery. The administration of propofol (120-240 mins) did not produce any of these changes. No patients required blood transfusion during surgery, and the patients had not previously been treated with cancer chemotherapeutic agents. The administration of nitrous oxide (60-150 mins) to patients undergoing orthopedic procedures did not affect blood L-methionine. It is concluded that the administration of nitrous oxide to cancer-bearing patients, but not to those undergoing orthopedic surgery, produced major changes in amino acid metabolism; therefore, consideration should be given to the avoidance of exposure of cancer patients to nitrous oxide.