The authors investigated the effect of prior administration of halothane upon the metabolism of enflurane. Twenty-four, one-year-old male, Fischer 344 rats were assigned randomly to four anesthetic exposure groups. Groups 1 and 2 were controls exposed only to halothane and enflurane, respectively. Group 3 was exposed for 1 h to 0.3% halothane, followed by 2 h of 1% enflurane. Group 4 was exposed for 1 h to 1% halothane and then to 2 h of 1% enflurane. Blood samples were taken prior to, immediately following, and 1, 24, and 48 h after anesthetic exposure. Serum was assayed for inorganic fluoride (F-), SGOT and SGPT. Twenty-four-hour urinary collections were assayed for F excretion. Group 1 rats exposed to halothane alone had the lowest peak mean serum F- (5.0 microM). Group 2 rats exposed to enflurane alone had the highest serum F concentration 4 h after anesthesia (18.7 microM). Peak serum F in Group 3 rats (9.5 microM) was significantly lower than in Group 2 rats (enflurane control). In Group 4 rats, serum F- was not significantly different from Group 1 rats (halothane control) at any time. In the first 24 h after anesthetic exposure, urinary F- excretion in Groups 2 and 3 was significantly higher than in Groups 1 and 4. This study demonstrated that prior exposure to halothane reduced the metabolism of enflurane; previous work suggested that this was due to an interaction of halothane with hepatic cytochrome P-450.(ABSTRACT TRUNCATED AT 250 WORDS)