The authors examined the effects of large intravenous doses of sufentanil (5–160 μg/kg) on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo,) in rats. CBF and CMRo2were measured by a modified Kety-Schmidt technique using135Xenon washout. Progressive decreases in CBF and CMRo2occurred in animals receiving sufentanil. The maximum decrease was 53% and 40% for CBF and CMRo2, respectively, at a dose of 80 μg/kg. The values for CBF and CMRo2in this group were 105 ± 10 ml · 100 g−1· min−1(mean ± SEM) and 6.5 ± 0.5 ml · 100 g−1· min−1, respectively, compared with 226 ± 28 ml · 100 g−1· min−1and 10.9 ± 1 ml · 100 g−1· min−1in the control group, which received N2O 70% in oxygen. Larger doses of sufentanil did not cause further significant changes in CBF and CMRo2. Sharp waves appeared on the electroencephalogram (EEG) of all the animals following sufentanil injection, and some animals had EEG changes develop consistent with seizure activity. This seizure-like activity appeared to consist of a single episode of short duration in the groups receiving 5, 10, and 20 μg/kg sufentanil. The incidence and frequency of seizure activity increased in the groups receiving higher doses of sufentanil, although the duration of seizures was still short. The results of this study indicate that sufentanil causes a significant decrease in CBF and CMRo2similar to that previously reported for fentanyl, and high doses of sufentanil may cause frequent seizure-like patterns appearing on EEG.