A comparison of the effects of thiopental or fentanyl with those of inhaled anesthetics requires the establishment of a comparable level of anesthetic potency. Accordingly, using the response of male Sprague-Dawley rats to tail-clamping, we determined the ED50S for thiopental and fentanyl. Half of the rats were pretreated with phenobarbital. After subcutaneous injection of various doses of thiopental or fentanyl, each rat was tested for movement in response to tail-clamping at 15-min intervals for 2 h. In untreated rats, the maximal effect of thiopental (i.e., the lowest ED50 value was 107 +/- 10 mg/kg, mean +/- SEM) occurred 75 min after injection. Although higher values were found at other times, differences from the nadir were relatively small. In rats pretreated with phenobarbital, the lowest value (130 +/- 8 mg/kg) occurred at 60 min. The lowest ED50S for fentanyl (52 +/- 7 micrograms/kg for control rats, and 73 +/- 14 micrograms/kg for pretreated rats) were found at 15 min.