A consecutive series of 105 outpatients with Parkinson's disease (PD) were examined for the presence of depression. Twenty-one percent met diagnostic criteria for major depression, 20% had minor depression, and the remainder were not depressed. The frequency of depression showed a bimodal distribution over time, with highest frequencies occurring in the early and late stages of the disease. Although other factors such as a positive family history of psychiatric disorders, quality of social functioning, and severity of tremor, rigidity, and akinesia did not show a significant association with depression, depressed patients had significantly higher impairment scores in activities of daily living and cognitive function than nondepressed PD patients. There was also a significant correlation between impairment and depression scores. In addition, among patients with mainly unilateral symptoms, depression was significantly associated with greater left hemisphere involvement. These findings suggest that depression in the early stages of the disease may be related to left hemisphere dysfunction, while later in the disease, depression and impairment in activities of daily living are interrelated. This may indicate more than one etiology of depression or that depression may have an adverse impact on the course of the disease.