Clinically, several symptoms are thought to be good indicators of illness severity, including sleep disturbance, weight loss, adhedonia and suicidal thoughts. The aim of this study was to identify individual items on the Beck Depression Inventory (BDI) and on the Hamilton Rating Scale for Depression (HRSD) that are most strongly associated with total severity. 361 subjects who met criteria for unipolar, primary major depression (DSM-III-R, RDC) were included in the analysis. Global severity of depression was assessed using the total scores on both the BDI and HRSD. Two stepwise regression analyses were performed to identify the items on each instrument that best predicted global severity. Nine BDI variables and 11 HRSD variables accounted for 90% of the variance in global severity on each instrument. Three items accounted for 67% of the variance on the BDI: Self Hate accounted for 35%, Loss of Interest for 20%, and Sadness for 11%. Two items accounted for 47% of the variance on the HRSD: Somatic Anxiety (31%) and Work/Interest (16%). Suicidal ideation accounted for only a small amount of variance on both the HRS-D (4%) and the BDI (1.4%). These findings confirm previous work that the two scales capture different aspects of depression: the cognitive/affective domain for the BDI and the vegetative domain for the HRS-D. Loss of interest accounted for substantial variance on both instruments and more variance than depressed mood. These data lend empirical support to the clinical position that anhedonia is the sine qua non symptom in depression.