The relative roles of the superoxide and hydroxyl radicals in oxidative stress‐induced neuronal damage were investigated using organotypic hippocampal slice cultures. Cultures exposed to 100 µM duroquinone, a superoxide‐generating compound, for 3 h developed CA1‐selective lesions over a period of 24 h. The damage accounted for ∼64% of the CA1 subfield, whereas CA3 showed just 6% damage, a pattern of damage comparable to that observed following hypoxia/ischaemia. Duroquinone‐induced damage was attenuated by a spin‐trap agent. In contrast, hydroxyl radical‐mediated damage, generated by exposure to 30 µM ferrous sulphate for 1 h, resulted in a CA3‐dominant lesion. The damage developed over 24 h, similar to that observed with duroquinone, but with ∼45% damage in CA3 compared with only 7% in CA1. These data demonstrate a selective vulnerability of the CA1 pyramidal neurones to superoxide‐induced damage and suggest that of the free radicals generated following hypoxia/ischaemia, superoxide, rather than hydroxyl radical, is instrumental in producing neuronal damage.