BACKGROUND: We set out to measure the impact of depression and its clinical resolution on patients' functional status. METHOD: The Work and Social Disability Scale (WSDS), a five-category investigator-rated scale measuring patient functional status, was completed at baseline and study discontinuation in a 56-day, open, uncontrolled study evaluating the safety of a sustained release (SR) formulation of bupropion in 3167 patients at 105 sites. To be included in the study, patients had to be 18 years or older, have a diagnosis of depression, and be considered appropriate for treatment with bupropion SR. The proportion of patients in each WSDS category, for those patients taking more than 7 days of bupropion SR (N = 2915), was assessed at screen and study discontinuation. The percentage of patients with improved WSDS scores at 56 days was also measured for all patients and correlated with patient and treatment characteristics. RESULTS: Of the patients entering the trial, 61.8% were markedly or severely impaired in their work or social activities, and only 5.4% were mildly or not impaired. At study discontinuation, more than 54% of patients were judged by the investigator to have very much or much improvement in their clinical symptoms. Results on the WSDS correlated with the clinical improvements; only 22.3% were markedly or severely impaired; and 50.0% were mildly or not impaired at study discontinuation. In addition, 63.9% of patients had less work or social disability at the end of the trial than at study entry. Functional status improved more in patients who had not previously been treated for the episode, had more severe depression at study entry, and had a higher dose and duration of treatment with bupropion SR. CONCLUSION: The results show that depression results in significant impairment in patients' functional status. Functional status improved in patients treated with bupropion SR for up to 56 days. This improvement was highly correlated with improvement in clinical symptoms and was related to patient characteristics at study entry as well as to treatment patterns during the study.