Measuring depression in patients with chronic illnesses such as multiple sclerosis (MS) is potentially complicated by the fact that several somatic symptoms of depression are also common in chronic illnesses. Whether standard assessment measures such as the Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HRSD) should exclude certain somatic symptoms when used in MS has been examined previously, but there is no clear consensus on this issue. The present study evaluated the utility of individual BDI and HRSD items for assessing depression in MS patients by examining how individual items responded to depression treatment in 42 (29 female) depressed MS patients. All 21 BDI items and 12 of 17 HRSD items decreased significantly with treatment, suggesting that all BDI items tap depression, as do 12 of 17 HRSD items. Thus, the present data support the inclusion of all BDI items when measuring depression in MS. Decisions on whether or not to use all HRSD items or only the 12 shown here to capture depression may depend on the study purpose and design.