The authors studied depression after focal subcortical lesions (SCLs) in 45 highly selected subjects. Secondary major depression (secondary MD) occurred in 20.0%, depressive disorder NOS (secondary DDNOS) in 4.4%, and secondary dysthymia in 0.0%. secondary MD after SCLs was associated with pallidal lesions (88.9%) and dystonia without geste antagonistique; subjects with secondary DDNOS had nigrotegmental lesions and parkinsonism. Depressive severity after SCLs correlated positively with severity of parkinsonism and dystonia. Pallidal lesions disrupting neurotransmitter systems and pallidothalamic and parietal input to the frontal lobe may lead to secondary MD, whereas nigrotegmental lesions may predispose to secondary MD forme fruste (secondary DDNOS) through disruption of mesocortical frontal or nigrostriatal dopamine tracts. Patients should be closely followed over several years for depression after such lesions, especially when accompanied by parkinsonism or dystonia without geste antagonistique.Abstract Teaser