The inhibitory effect of intrathecal (i.th.) fentanyl on spinal reflexes in rabbit is reduced after blockade of spinal α₂-adrenoceptors with RX 821002 (100 µg i.th., Clarke et al., 1998). Thus, it appears that activity in spinally-projecting adrenergic neurones facilitates the efficacy of spinally-applied fentanyl. In the present study we have investigated the dose of RX 821002 necessary to produce this effect in decerebrated rabbits with and without acute inflammation of the ipsilateral metatarsophalangeal joints. Twelve rabbits were decerebrated under isoflurane (2 – 5 %)/N₂O anaesthesia. Of these, 5 had been immunized against ovalbumin over the preceding 28day period (Harris and Clarke, 2003). Reflexes were evoked in the medial gastrocnemius (MG) muscle nerve by electrical stimulation of the skin at the heel using pulses of 10 mA, 1 ms. Responses were averaged and integrated by computer, and analyzed in 3 time bands relative to the stimulus: 5 – 20 ms (phase 1); 20 – 120 ms (phase 2) and 120 – 250 ms (phase 3): only data from phase 1 recordings are reported here. Fentanyl and RX 821002 were given alternately 30 – 40 min intervals. The dose of fentanyl was fixed at 3 µg kg^-1 i.th., with the doses of RX 821002 at 3, 7, 20 and 70 µg kg^-1 i.th. (cumulative dose 100 µg kg^-1) interposed between each injection of opioid. In the 5 immunized animals, this protocol was performed 3 – 6 h after injection of 5 mg ovalbumin in 100 µl of 0.9% saline at the ipsilateral metatarsophalangeal joints (Harris and Clarke 2003) to induce an acute inflammation. Experiments were terminated by i.v. injection of saturated KCl solution.In control animals before RX 821002 fentanyl inhibited MG reflexes to a median of 7% (inter-quartile range, IQR, 6 – 29%, n = 7) of pre-fentanyl values. After RX 821002 10 µg kg^-1 cumulative dose, this effect was significantly decreased so that the opioid suppressed reflexes to a median of 63% (IQR 42 – 75%, Wilcoxon test, p < 0.04) of immediate pre-fentanyl values. In inflamed animals before RX 821002, fentanyl inhibited MG responses to a median of 75% (IQR 47 – 87%, n = 5) of pre-fentanyl levels, a significantly smaller effect than observed in non-inflamed animals (Mann-Whitney test, p < 0.02). After RX 821002 10 µg kg^-1 cumulative, fentanyl reduced reflexes to a median of 28% (IQR 3 – 72%) of immediate pre-fentanyl values, not significantly different from the pretreatment effect (Wilcoxon, p > 0.1).These data confirm that the effects of intrathecal fentanyl are supported by endogenous noradrenaline, but that this support is lost in conditions of acute antigen-induced inflammation.