Diving birds and mammals routinely encounter severely hypoxic conditions, which they cope with through several hypoxia-protective adaptations. These were recently shown in the hooded seal to include an enhanced neuronal hypoxia tolerance (Folkow et al. 2008). Here we have made extracellular recordings of spontaneous activity (SA) in the Purkinje cell layer of isolated cerebellar slices and compared neuronal responses to 60 min hypoxia (H; 95% N₂, 5%CO₂), alone or in combination with chemical anoxia (NaCN), in a diving bird (common eider duck) versus a non- diving bird (chicken) and a mammal (rat). Three typical responses were seen: SA disappeared but recovered (R) or failed to recover (NR) during re-oxygenation, or SA persisted (P) throughout the insult, albeit at a lower level. We found that the proportions of slices that survived (R+P) in H+NaCN was significantly higher (p<0.007) for ducks (100%) than for chicken (63%), and also for the ducks/chicken than for rats (0%), and that the mean SA level in R slices was significantly higher (p<0.003) in ducks (20.2±22.0%) than in chicken (3.0±2.7%). This implies that duck cerebellar neurons have higher hypoxia tolerance than those of chicken, due to higher anaerobic capacity. Duck slices that were exposed to H+NaCN and the K⁺_ATP- blocker tolbutamide did not display recovery that was significantly different from controls, suggesting these channels are less important in the hypoxia defence. Lessons learned from studies of neuro-protective mechanisms of hypoxia-tolerant diving animals may potentially help guide efforts to find effective treatments of hypoxic injury in man. Folkow, L.P., Ramirez, J.-M., Ludvigsen, S., Ramirez, N. & Blix, A.S. 2008. Neurosci Lett 446,147–150