Depression is a common finding in patients with Parkinson's disease (PD). Traditionally, depression has been treated with tricyclic antidepressants, which are often associated with undesirable side effects that may limit their use in PD. Few studies have been performed with selective serotonin reuptake inhibitors (SSRIs) in these patients. We assessed the tolerability of the SSRI antidepressant paroxetine (10-20 mg once per day) in 65 outpatients with PD and depression for a period of at least 3 months. Treatment was continued for 125.3+/-89.6 days (mean +/- standard deviation) in 52 patients. In these subjects the Hamilton Disease Rating Scale improved from 21.7+/-6.4 to 13.8+/-5.8 (p <0.001). Overall, 13 patients stopped paroxetine after 9.6+/-10.6 days because of adverse reactions. Two patients reported increased "off" time and tremor that reversed after treatment was stopped. No risk factors for intolerance were identified. Paroxetine is a safe and effective drug to treat depression in PD.