Background: To investigate the effects of disability and specific treatments on depression associated with multiple sclerosis (MS). Methods: Fifty-two patients with MS (patient group) and 48 healthy subjects (control group) participated in the study. While the Beck Depression Inventory (BDI) and the Expanded Disability Status Scale (EDSS) were administered to the patients, healthy controls filled out only the BDI. Psychiatric disorders were determined using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Result: Both groups were found to be identical in their socio-demographic properties. The mean age of onset of MS was 29.1±1.2 years. There was no difference between males and females in terms of depression. The patient group consisted of patients with: relapsing-remitting MS (71.2%), secondary-progressive MS (13.5%), progressive-relapsing MS (11.5%), and primary-progressive MS (3.8%). A 12-fold increased risk for depression was found among patients with MS. Age, attack number and illness duration did not correlate significantly with risk for development of depression in MS. However, a significant relationship was found between EDSS scores and the risk for the development of depression. Depression was detected in patients using azathioprine (100%), interferon beta-1a SC (88.8%) and in patients not receiving any treatment (78.5%). Conclusion: This study indicates that, disability is an important risk factor for the development of depression, irrespective of the treatment modality. © Archives of Neuropsychiatry, published by Galenos Publishing.