Methods: Tracheal rings from adult, male, Dunkin− Hartley guinea− pigs were incubated for 4 days in saline or TNF− α (100 ngml) for a-1 comparison of the contractions to the muscarinic receptor agonist, methacholine, or to a range of frequencies of electrical field stimulation (EFS; 0.1− 30 Hz frequency, 1 min trains every 2 mins, 0.5 ms pulse width and 20 V) or repetitive EFS (5Hz frequency, 10 sec trains every 100 sec, 0.5 ms pulse width and 20 V). Data are given as mean±SEM of n= 6 animals. Results: Following incubation for 4 days with TNF− α, contractions of the trachea to methacholine were not different to those incubated with saline. In contrast, contractions of the TNF− α incubated trachea to EFS over the 0.1–30Hz frequency range were greater than those incubated with saline. The EFS-evoked contractions were abolished by 10 M of tetrodotoxin or atropine but not hexamethonium,-6 whereas the methacholine-evoked contractions were abolished by only atropine. The presence of 10 M of-6 D9-THC, CP 55940 or CBD did not alter the contractions of either TNF− α-or saline-incubated trachea to methacholine. However, D9-THC and CP 55940, but not CBD, inhibited the EFS-evoked contractions enhanced by TNF− α to the height of the saline-incubated trachea. Under repetitive EFS conditions, both D9-THC and CP 55940 inhibited the contractions of only the TNF− α-incubated trachea with a similar maximum of 90.3±3.76 and 86.9±6.01% respectively, and pEC of 8.34±0.13 and 7.65±0.10, respectively. This inhibition was antagonised by the CB receptor