BACKGROUND: When using a target controlled infusion (TCI) of propofol, combination with N2O or fentanyl as an analgesic adjuvant is common in clinical practice. In a previous study, a minimal steady state plasma concentration necessary to prevent a response in 50% of the patients following a skin incision (Cp50i) for propofol was reduced from 6ng/ml to 4.5ng/ml with 67% nitrous oxide/oxygen compared to air/oxygen. The goal of this study was to quantify the effect site concentration of fentanyl required to replace 67% N2O at a propofol effect site target concentration of 4.5ng/ml. METHODS: Forty six ASA class I or II adult patients scheduled for lower extremity surgery were randomly allocated to one of three groups according to assigned effect site concentration of fentanyl. Group 1, n = 15; 0.5 ng/ml, Group 2, n = 15; 1.0 ng/ml, Group 3, n = 15; 1.5 ng/ml. Patients received propofol with target concentration 4.5ng/ml and predetermined target concentration of fentanyl in three groups. A laryngeal mask airway was placed after anesthesia induction and all patients were controlled ventilation with 67% air/33% oxygen. The response to the skin incision was observed and the patients categorized as movers or non-movers according to Eger's criteria. Cp50i for fentanyl was evaluated using nonlinear regression analysis. RESULTS: Non-movers to skin incision was 20%, 43.7%, 73.7% in groups 1 3 respectively. Cp50i for fentanyl combined with propofol 4.5ng/ml was 1.08 ng/ml. CONCLUSIONS: We concluded that the MAC for 67% N2O is equivalent to an effect site target fentanyl concentration of 1.08 ng/ml in terms of no movement to skin incision.