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The magnitude and duration of analgesia and respiratory depression induced by fentanyl (1.0, 2.0, and 4.0 micrograms/kg) and sufentanil (0.1, 0.2, and 0.4 microgram/kg) after intravenous administration over 30 s were measured in 30 healthy young adult male volunteers divided into three groups and studied in a double-blind, randomized fashion. Each volunteer received one dose of fentanyl or sufentanil and no sooner than 48 h later, the corresponding equipotent dose of the other opioid. End-tidal CO2 and ventilatory and occlusion pressure responses to CO2 rebreathing were used to measure drug-induced respiratory effects. Analgesic effects were assessed by changes in the pain threshold to electric shock applied to the forearm. Plasma levels of fentanyl and sufentanil were measured by radioimmunoassay. Testing and sampling intervals were 5, 30, 60, 90, 120, 240, 300, and 360 min after drug administration. The magnitude and duration of depression of the ventilatory and occlusion pressure response were significantly less with sufentanil compared with fentanyl, irrespective of dose. Ventilatory and occlusion pressure responses returned to control values by 30 and 30 min, respectively, after sufentanil and by 240 and 120 min, respectively, after fentanyl. Statistically significant elevations of the pain threshold were, however, greater and longer lasting after sufentanil compared with fentanyl. Pain threshold returned to control values 180 min after sufentanil but only 90 min after fentanyl. These results suggest that sufentanil may provide better patient comfort with less respiratory depression than does fentanyl.