The binding of tritiated imipramine was significantly reduced in the hippocampus and occipital cortex from a series of patients with depressive illness compared with age-matched patients with no psychiatric disorder. In contrast there was no change in imipramine binding in established cases of senile dementia of Alzheimer-type. Scatchard analysis indicated normal binding affinity but a reduction in the number of imipramine binding sites in depression. These observations parallel previous findings of decreased binding sites in platelets from depressed patients and suggest there may be an abnormality in the uptake mechanism for serotonin in depression.