We investigated whether fentanyl decreases the serum concentrations of the steroid anesthetic eltanolone effective in producing loss of consciousness in 50% of patients (EC(50induction)) and in preventing movement at skin incision in 50% of patients (EC(50incision)). For anesthetic induction, patients received effect-site target concentrations of fentanyl 0.0, 1.5, 3.0, or 4.5 ng/mL and eltanolone 500, 750, 1000, or 1200 ng/mL. Loss of response to verbal command was assessed after 10 min. For incision, patients received effect-site target concentrations of fentanyl 0.5, 1.5, 320, or 4.5 ng/mL and eltanolone 547-2926 ng/mL. Movement at incision was assessed at least 10 min after new targets were entered. Probability of loss of consciousness and of movement versus arterial serum concentration combinations were analyzed by logistic regression. Dixon updown analysis was used to estimate ET(50incision) effective target concentration combinations. In the absence of fentanyl, anesthesia was induced in only 1 of 12 patients, which suggests that the EC(50induction) is >1500 ng/mL at fentanyl 0.0 ng/mL. With fentanyl (38 patients), eltanolone EC(50induction) was independent of fentanyl concentration, calculated as 628 ng/mL. For the incision phase (52 patients), logistic regression failed to generate a valid model. Dixon analysis (43 patients) produced an eltanolone ET(50incision) of 2288 ng/mL at fentanyl targets of 0.5 ng/mL, 754 ng/mL at 1.5 ng/mL, 735 ng/mL at 3.0 ng/mL, and 645 ng/mL at 4.5 ng/mL. Fentanyl reduced the serum concentration of eltanolone required to produce loss of consciousness and the target concentration of eltanolone required to prevent movement to skin incision. Implications: Fentanyl reduced the serum concentration of eltanolone required to produce loss of consciousness and the target concentration of eltanolone required to prevent movement to skin incision. Future interaction studies of this nature using logistic regression should model responses to hypnotic alone separately from responses to hypnotic-analgesic combinations.