[3H]Imipramine binds with high affinity to membranes from different regions of the human brain. The highest density of binding sites was observed in the hypothalamus and substantia nigra and the lowest density in the white matter and cerebellum. As found in rat brain, tricyclic antidepressant drugs are potent inhibitors of [3H]imipramine binding. Atypical antidepressants are, however, much weaker at inhibiting the specific binding. The [3H]imipramine binding site in human cortex is apparently identical to the site already described in the rat brain and in human platelets.