Background: The object of this study was to test whether substituting part of the methohexital dose with the short-acting opioid remifentanil would prolong seizure duration in middle-aged patients while providing a similar depth of anesthesia as with methohexital alone. This has been reported for the combined use of methohexital and remifentanil in elderly patients, but has not been investigated in middle-aged patients likely to require a higher total dose of methohexital for inducing anesthesia. Method: Seven patients (42±10 years; mean ±SD) receiving electroconvulsive therapy (ECT) were anesthetized with methohexital (1.25 mg kg−1) or with methohexital (0.625 mg kg−1) plus remifentanil (1 µg kg−1) in this randomized, double blind, crossover study. Additional methohexital was given as needed until loss of eyelash reflex was observed. Suxamethonium (1 mg kg−1) was used for muscular paralysis. Results: Motor and EEG seizure durations were significantly longer after induction with methohexital plus remifentanil (45±14 and 58±15 s) than with methohexital alone (31±11 and 42±18 s). A methohexital dose of 1.2±0.3 and 1.9±0.3 mg was necessary to achieve loss of eyelash reflex if methohexital was used with and without remifentanil. Peak heart rate after ECT was significantly higher if remifentanil was coadministered with methohexital (148±12 vs. 126±24 b.p.m). Conclusion: Substituting part of the methohexital dose with remifentanil is a useful anesthetic technique to prolong seizure duration in middle-aged patients requiring a 1.5-fold higher induction dose of methohexital than elderly patients, the only population studied to date for the combined use of methohexital and remifentanil in ECT.