To design an efficient infusion regimen from pharmacokinetic data, it is necessary to know the alfentanil plasma concentrations required for satisfactory anesthesia. In 37 patients about to undergo lower abdominal gynecologic, upper abdominal, or breast surgery, anesthesia was induced with alfentanil 150 μg/kg iv and 66% N2O in oxygen. Thereafter, N2O anesthesia was supplemented with a continuous infusion of alfentanil that was varied between 25 and 150 μg · kg-1 · h-1, as indicated by the patient's responses to surgical stimulation. Small bolus doses of alfentanil 7 or 14 μg/kg were administered and the infusion rate increased to suppress precisely defined somatic, autonomic, and hemodynamic responses. Arterial plasma concentrations of alfentanil were measured during the operation when the patient did and did not respond to noxious stimulation. Logistic regression was used to determine plasma concentration–effect curves for different stimuli. Plasma alfentanil concentrations required along with 66% N2O to obtund responses to single episodes of stimulation in 50% of the 37 patients (Cp50 ± SE) were: 475 ± 28 ng/ml for tracheal intubation, 279 ± 20 ng/ml for skin incision, and 150 ± 23 ng/ml for skin closure. Between skin incision and closure, multiple determinations of response/no response were made for each patient and an individual Cp50 was estimated. The Cp50 (mean ± SD) for the three surgical procedures were: breast, 270 ± 63 ng/ml (n = 12); lower abdominal, 309 ± 44 ng/ml (n = 14); and upper abdominal, 412 ± 135 ng/ml (n = 11). The Cp50 for satisfactory spontaneous ventilation after the discontinuation of N2O was 223 ± 13 ng/ml. These data demonstrate that different perioperative stimuli require different alfentanil concentrations to suppress undesirable responses. Thus, the alfentanil infusion rate should be varied according to the patient's responsiveness to stimulation in order to maintain satisfactory anesthetic and operative conditions and to provide rapid recovery of consciousness and spontaneous ventilation.