Smooth pursuit eye movement (SPEM) dysfunction is a putative genetic marker for schizophrenia, but it has also been described in major depression. The authors longitudinally evaluated effects of clinical state on SPEM quality in patients with depression. Prior to ECT, SPEM abnormality characterized 42% of 24 severely depressed patients, 60% of 30 schizophrenia patients, and 5% of 20 control subjects. SPEM was significantly correlated to Hamilton Rating Scale for Depression scores (r = 0.49, P = 0.02) in the depressed patients. Although SPEM was transiently disrupted by an acute ECT treatment, it improved during the treatment course. This improvement of SPEM quality with clinical recovery suggests that SPEM abnormality may be a state marker in severe major depression, in contrast to its invariable trait nature in schizophrenia.