Reports of the lack of protection following oral dantrolene prophylaxis have led some authors to recommend only intravenous administration of dantrolene for prophylaxis against malignant hyperthermia at induction of anesthesia. The authors determined whether a specific regimen of preoperative oral dantrolene would result in protective blood levels at induction of anesthesia, and in the postoperative period. Ten malignant hyperthermia-susceptible (MHS) patients were given a total dose of 5 mg.kg-1 of oral dantrolene in three or four divided doses, every 6 h, with the last dose 4 h preoperatively. Plasma dantrolene levels were determined by reverse phase high pressure liquid chromatography at induction of anesthesia and every 6 h thereafter for 48 h. All ten patients had plasma dantrolene levels over 2.8 micrograms.ml-1 at induction of anesthesia, for at least 6 h and, in three patients, up to 18 h after induction. Every patient had an uneventful perioperative course. Side effects (drowsiness, weakness) occurred in seven patients. An elimination half-life of 15.8 +/- 6.0 h was determined. In contrast to intravenous dantrolene, this specific oral dantrolene regimen resulted in protective plasma levels for 6-18 h after induction of anesthesia. These results were likely due to the relatively high bioavailability of oral dantrolene and, possibly, to continued absorption of dantrolene in the postoperative period.