Under the same environmental conditions and inoculum load, a northern New South Wales provenance of Eucalyptus nitens (Deane and Maiden) Maiden is more resistant to Mycosphaerella leaf disease than a southern New South Wales provenance. Using histological methods, a comparison was made between one provenance from each distribution with respect to constitutive anatomy and cellular and histochemical changes after infection by Mycosphaerella species that cause Mycosphaerella leaf disease. Leaves from the resistant provenance were significantly thinner, had a higher proportion of palisade mesophyll and reduced intracellular airspace compared with those from the susceptible provenance. After infection, an increased level of cell division was observed in resistant leaves and the necrophylactic periderm formed was more organised, continuous, suberised and lignified than periderm formed in susceptible leaves. It is suggested that leaves with higher constitutive proportions of cell dense palisade layers and thinner leaves can partition infected leaf sections from healthy tissue more effectively as less cellular differentiation is required to form an effective necrophylactic periderm. Palisade layers with less intercellular airspace may also play a role in the slowing or prevention of infection as some Mycosphaerella species may not be able to penetrate tightly packed cells.