Raised tissue iron levels in the substantia nigra in Parkinson's disease (PD) suggests that altered iron homeostasis may underly the disorder. We have therefore investigated the distribution of non-haem iron in the normal and PD substantia nigra, using a sensitive histochemical procedure, to assess the pathogenic potential of this metal. In control cases non-haem iron staining was highest in the substantia nigra zona reticulata (SNr) and associated with the neuropil, oligodendrocytes, astrocytes and non-pigmented neurones. The substantia nigra zona compacta (SNc) showed lower non-haem iron staining than the SNr, with generalized impregnation of the neuropil and occasional non-haem iron-positive oligodendrocytes and astrocytes. The pigmented dopaminergic neurones were unstained, often present in areas of neuropil with low iron reactivity. In PD the SNc showed increased iron staining of the neuropil with many iron-positive microglial cells associated with extracellular melanin. The remaining dopaminergic neurones were unstained, though many of the non-pigmented neurones of the SNr were iron-positive.