Several authors have reported enlarged lateral brain ventricles in major depressive patients as compared to healthy controls. Also, the enlargement of brain lateral ventricles has been related to delusions, psychomotor retardation and some biochemical data such as cortisol secretion and L-tryptophan serum levels. The present study was undertaken to investigate if melancholic depressives are characterised by a higher degree of brain atrophy than normal controls and minor depressives, the origin of any brain atrophy, and whether measures of brain atrophy are related to cortisol secretion and L-tryptophan serum levels. We investigated 10 healthy controls and 35 depressive patients categorised according to DSM-III. In contrast to previous studies, we determined a combination of indices which makes it possible to differentiate between central and cortical diffuse atrophy. We found no evidence for the existence of abnormal atrophy of the brain in melancholics; nor did we find any correlation between CT scan measurements and cortisol or tryptophan.