The association of post-stroke depression (PSD) and site of cerebral lesion was investigated in 117 patients with first-ever stroke in the Perth Community Stroke Study, who were depressed 4 months post-stroke. The site of lesion was previously localised by studying the CT scan in conjunction with the atlas of neuroanatomy and cranial computed tomography of Kretschmann and Wainrich, rather than the topographical approach used in most previous studies. Patients who were depressed immediately prior to the stroke were excluded. No support was found for the assertion that lesion location is a prime factor in the aetiology of PSD. Future investigations of this topic should encompass a much broader range of variables than lesion location, as the aetiology of PSD is likely to be multi-factorial.