question: BACKGROUND An increasing number of patients come to the operating room in use of opioid analgesics. They have different levels of tolerance to opioid effects which challenge the anesthesiologists in search of safe and effective opioid dosing perioperatively. The tested hypothesis is that simple measures introduced will allow us to measure tolerance qualitatively. Opioid effects on pain (analgesia) and dyspnea sensations (relieving effect) are tested. Patients were allocated to three groups according to pre-operative analgesics: (1) control, without any opioid analgesics, (2) weak opioid, and (3) strong opioid. Pressure pain threshold (PPT) and no-respiratory sensation period (NRSP) were measured at two points: before and 3 min after intravenous fentanyl administration. RESULTS A total of 58 (43 controls, 9 weak opioids, and 6 strong opioids) patients were enrolled. PPT and NRSP, after iv 2 μg/kg ideal body weight (IBW) fentanyl, were significantly elevated in the control patients (PPT: 6.2 ± 2.1 N to 9.2 ± 3.9 N, p < 0.0001, NRSP: 17.8 ± 10.8 s to 22.8 ± 18.7 s, p < 0.005, paired t test). However, preoperative opioid use, though with tendency, did not show a significant decrease of the opioid effect. Due to an insufficient number of participants, no conclusion could be drawn. Further analysis of the data from control patients showed a significant difference between the two sexes in sensitivity to PPT and NRSP, as well as fentanyl effect on PPT. CONCLUSIONS Current data showed a simple method of measuring the opioid effect on two dimensions: pain and respiration. Though not able to show a qualitative measurement of tolerance formation in opioid-users, data from control patients showed females to be more sensitive to pain and dyspnea but is less sensitive to the opioid effect. Further studies are necessary to show whether these gender differences serve as clinical relevance. TRIAL REGISTRATION UMIN, UMIN 000011580. Registered 27 August 2013, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013352&language=J.