BACKGROUND: Major Depressive Disorder is widely recognised to be a heterogeneous syndrome with numerous depressive phenotypes, one of which is melancholic depression. Patients with melancholic depression exhibit treatment responses and outcomes that differ from patients with non-melancholic depression. The current study aimed to assess whether differences existed between melancholic and non-melancholic subtypes of depression, as measured by the event related potential, intensity dependence of the auditory evoked potential (IDAEP). METHODS: IDAEP was assessed in 14 melancholic and 13 non-melancholic depressed subjects and 14 controls. RESULTS: The melancholic patients had a significantly shallower IDAEP slope than the non-melancholic patients not explained by depression severity or age. LIMITATIONS: Antidepressants were taken by all patients in this study and the effect of continual use of these drugs on the IDAEP slopes has yet to be confirmed. CONCLUSIONS: These results provide support for neurobiological differences between melancholic and non-melancholic depressive subtypes. Melancholic depression may be characterized by ongoing over function of the serotonin system in spite of medication treatment.